tbuckley/cabot-search huggingface dataset:
SAT0349 Relationships between changes in bone mineral density and vertebral fractures incidence: An analysis of the last 2 years of a 10-year treatment with strontium ranelate
Authors: O. Bruyere, J.-Y. Reginster
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> We have previously shown that, in women treated for 3 years with strontium ranelate, an increase in hip bone mineral density (BMD), but not spine BMD, was associated with a proportional reduction in vertebral fracture incidence (Bruyere et al, Journal of Clinical Endocrinology and Metabolism, 2007). As a matter of fact, each 1% in femoral neck or total proximal femur BMD was associated with decreased risk to experience a new vertebral fracture by 3% (95% adjusted CI 1%&gt;5%) and 2% (1%&gt;4%), respectively. Some women have now been treated for 10 years with strontium ranelate. <h3>Objectives</h3> Our objective is to assess the relationship between change in BMD and vertebral fracture incidence in the last 2 years of the 10-year treatment. <h3>Methods</h3> We have included women from the strontium ranelate arm of the Spinal Osteoporosis Therapeutic Intervention study (SOTI) and the TReatment Of Peripheral OSteoporosis study (TROPOS) having received the treatment for 10 years. <h3>Results</h3> 116 women with femoral neck and total hip BMD and fracture data available during the 10 years of follow-up were included in the present analysis. During the last two years of follow-up, 12 patients experienced a new vertebral fracture. After having controlled for age, body mass index at year 9, BMD at year 9, number of vertebral fracture at year 0, number of new vertebral fracture from year 0 to year 8, we found that the BMD change at the femoral neck from years 9 to 10 was significantly associated with vertebral fractures incidence during the same period of time (p=0.03). Each 1% increase in femoral neck BMD was associated with a 15% (95% adjusted CI 2% to 26%) decreased risk to experience a new vertebral fracture. The same trend was observed for total hip BMD (7% [95%CI -3% to 17%) but it did not reach statistical significance (p=0.16). Women with new vertebral fractures from years 9 to 10 experienced during the same period a decrease of 2.4 (4.7) % in femoral neck BMD, compared to an increase of 1.5 (8.3) % in women without new vertebral fracture. <h3>Conclusions</h3> During the last 2 years of a 10-year treatment with strontium ranelate, the increase in femoral neck BMD was associated with a proportional reduction of the incidence of new vertebral fractures. These results confirm that the assessment of femoral neck BMD could be of interest to monitor women treated with strontium ranelate. <h3>Disclosure of Interest</h3> None Declared
Localized prostate cancer aggressiveness and low serum testosterone levels.
Authors: H. Botto, Y. Neuzillet, T. Lebret, P. Camparo, V. Molinie, C. Theodore, V. Hupertan, J. Raynaud
Journal: Journal of Clinical Oncology (2010)

e15005 Background: There is accumulating evidences that low testosterone (lowT) serum level in prostate cancer patients before treatment is associated with poor prognosis and that men with lowT prior to a medical castration had earlier tumor recurrences and higher tumor specific death rate. The aim of this observational study was to characterize the aggressiveness of the prostate cancer assessed by the Gleason score (GS) and the predominant Gleason pattern (pGP), in relation to preoperative testosterone serum concentration. Methods: 247 patients, referred to our Department (from 01/2007 to 12/2009) for a radical prostatectomy, had preoperative TT and Bioavailable Testosterone (samplings between 7 and 10 am) serum determinations (radio-immuno assayed in a central laboratory). GS and pGP was determined in prostate biopsies and prostate tissue specimens. Results: In biopsy specimens, a GS7 was observed in 105 (43%) of the patients; 25 (10%) had a pGP4. In prostate specimens, 163 (66%) had a GS7; 60 (24%) had a pGP4. For prostate specimens, comparing the 75 patients with a pGP4 (GS 4+3, 4+4 and 4+5) to the 172 with a pGP3 (GS 3+3 and 3+4), TT was lower (4.03 vs. 4.75 ng/mL, p=0.003) and PSA higher (11.1 vs. 7.3 ng/mL, p<0.00001). Extra prostatic extension and positive margins were more frequently observed (52% versus 18%, p<0.000001 and 29% versus 15%, p=0.009, respectively). The 40 patients with TT <3.0 ng/mL were bigger (+5kg, BMI + 1.7 kg/m2), PSA was higher (9.9 vs. 8.2 ng/mL, p=0.07). They had a higher percent of GS with a pGP4: 53% vs. 25% (p=0.0008). Conclusions: The aggressiveness of the tumor cannot be properly estimated by the GS and pGP found in biopsies. The pGP in prostate specimens is of paramount importance, especially in case of a Gleason 7, to appreciate the outcomes and to choose the treatment. Preoperative testosterone should be added to PSA determination to improve prediction of prognosis of treatment. No significant financial relationships to disclose.
Concomitant treatment of brain metastasis from non-small cell lung cancer with whole brain radiotherapy and gefitinib
Authors: S. Ma, Y. Xu, Q. Deng, X. Yu
Journal: Journal of Clinical Oncology (2008)

19135 Background: Brain metastases (BM) represent one of the most frequent complications related to non-small lung cancer (NSCLC), and their treatment continues to evolve. We have evaluated the activity, toxicity,the impact on Quality of Life (QoL) and survival of a concomitant treatment with whole brain radiotherapy (WBRT) and Gefitinib in patients with brain metastases from NSCLC in a phase II study. Patients and Methods: Between October 2005 and January 2007, 21 patients were enrolled and received 40 Gy/20f/4w WBRT with concomitant Gefitinib (250 mg/day). The primary end point of the study was response rate and QOL.The secondary end points were toxicity and survival. Results: 4 patients had a complete response, 13 patients had a partial response, 3 patients had stable disease, while 1 patient had progression disease. The overall response rate was 81.0%. The median progression-free survival and overall survival were 9.0 months and 13.0 months, respectively. The most frequent toxicities included rash (85.7%) and diarrhea (42.9%), and only 3 patients developed a grade 3 diarrhea. Gender and Cigarettes-year were found to be predictive factors for response in patients. There were statistically significant changes between pretreatment and post-treatment in all domains of QOL but additional concerns with the FACT- L. Multivariate survival analysis found that Adenocarcinoma and RAP groupingI were favourable prognostic factors. Conclusion: Our data suggest that this concomitant treatment was well tolerated, with promising activity and a significant improvement in quality of life. To allow comparisons across phase II trials, enrollment criteria may need to be restricted. No significant financial relationships to disclose.
Abstract 18448: Partial Blockade of Inwardly Rectifying K+ Current Enhances Electrotonic Interactions and Destabilizes Spiral Wave Reentry
Authors: Yasunori Kushiyama, Haruo Honjo, Ryoko Niwa, Hiroki Takanari, Masatoshi Yamazaki, Yoshio Takemoto, Ichiro Sakuma, Itsuo Kodama, Kaichiro Kamiya
Journal: Circulation (2012)

Introduction: Spiral wave (SW) reentry is a principal mechanism for the maintenance of tachyarrhythmias, such as ventricular tachycardia/fibrillation (VT/VF). We have recently reported that partial...
Micro-Organisms In Water.
Journal: JAMA (1894)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Prenatal Exposure to Phthalates and Anogenital Distance in Male Infants from a Low-Exposed Danish Cohort (2010–2012)
Authors: Tina Kold Jensen, Hanne Frederiksen, Henriette Boye Kyhl, Tina Harmer Lassen, Shanna H. Swan, Carl-Gustaf Bornehag, Niels E. Skakkebaek, Katharina M. Main, Dorte Vesterholm Lind, Steffen Husby, Anna-Maria Andersson
Journal: Environmental Health Perspectives (2015)

Phthalates comprise a large class of chemicals used in a variety of consumer products. Several have anti-androgenic properties, and in rodents prenatal exposure has been associated with reduced anogenital distance (AGD)-the distance from the anus to the genitals in male offspring. Few human studies have been conducted, but associations between the anti-androgenic phthalates and male AGD have been reported.We aimed to study the association between phthalate exposure in late pregnancy in Danish women pregnant in 2010-2012 and AGD in their male infants at 3 months of age (n = 273).In the Odense child cohort study, urinary concentrations of 12 phthalate metabolites of diethyl, di-n-butyl, diisobutyl, di(2-ethylhexyl), butylbenzyl, and diisononyl phthalate (DEP, DnBP, DiBP, DEHP, BBzP, and DiNP, respectively) were measured among 245 mothers of boys at approximately gestational week 28 (range, 20.4-30.4) and adjusted for osmolality. AGD, penile width, and weight were measured 3 months after the expected date of birth. Associations between prenatal phthalate and AGD and penile width were estimated using multivariable linear regression adjusting for age and weight-for-age standard deviation score.Phthalate levels were lower in this population than in a recent Swedish study in which phthalates were measured in the first trimester. No consistent associations were seen between any prenatal phthalate and AGD or penile width. Most associations were negative for exposures above the first quartile, and for ln-transformed exposures modeled as continuous variables, but there were no consistent dose-response patterns, and associations were not statistically significant (p > 0.05).We found no significant trends towards shorter AGD in boys with higher phthalates exposures in this low exposed Danish population.Jensen TK, Frederiksen H, Kyhl HB, Lassen TH, Swan SH, Bornehag CG, Skakkebaek NE, Main KM, Lind DV, Husby S, Andersson AM. 2016. Prenatal exposure to phthalates and anogenital distance in male infants from a low-exposed Danish cohort (2010-2012). Environ Health Perspect 124:1107-1113; http://dx.doi.org/10.1289/ehp.1509870.
Successes of the Healthy Hunger-Free Kids Act
Authors: Erin R. Hager, Lindsey Turner
Journal: JAMA Pediatrics (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Novel pathway of MDM2 stabilization by CARP2 that involves 14-3-3σ degradation
Authors: Wensheng Yang, Jiandong Chen, Wafik El-Deiry
Journal: Cancer Research (2008)

2776   CARP proteins (CARPs, including CARP1 and CARP2) are E3 ubiquitin ligases that promote the degradation of apical caspases of the extrinsic pathway and the p53 tumor suppressor protein (Yang et al., J. Biol. Chem. 282:3273-3281, 2007). To further examine CARP-mediated degradation of p53 we found that CARPs mediate MDM2 stabilization. Mutation of CARPs in the RING-domain abolished stabilization of but not binding to MDM2, indicating that stabilization of MDM2 by CARPs requires E3 ligase activity. Overexpression of CARP2, but not CARP1, caused degradation of endogenous 14-3-3σ whereas silencing of CARP2 induced stabilization of 14-3-3σ and associated reduction of MDM2 expression. CARP2 failed to stabilize but could still interact with MDM2 in 14-3-3σ knock-out cells. Silencing of MDMX did not affect CARP2-mediated stabilization of MDM2. Taken together, our data suggest that degradation of 14-3-3σ by CARP2 is mainly responsible for, though stabilization of MDMX by CARP2 may also contribute to, stabilization of MDM2 and subsequent elimination of p53.
ABT-263: An orally bioavailable Bcl-2 family protein inhibitor
Authors: Steven Elmore
Journal: Cancer Research (2007)

ND-1  The genetic instability inherent to cancer gives rise to defects in both cell growth and cell death pathways that facilitate tumor initiation and progression. Apoptosis is an evolutionarily conserved and highly regulated process that is the primary mechanism for the removal of damaged and unnecessary cells. One of the fundamental hallmarks of cancer is the ability to evade physiologic cues that would initiate this form of cellular suicide in normal cells. This is often accomplished through dysregulation of apoptotic signaling pathways. The Bcl-2 protein family regulates the intrinsic or mitochondrial apoptotic pathway through an array of interactions between pro-apoptotic (pro-death) and anti-apoptotic (pro-survival) family members. The anti-apoptotic proteins, such as Bcl-2 and Bcl-xL, act as checkpoints in this signaling cascade by binding and sequestering pro-apoptotic proteins thereby protecting cells from apoptosis. Cancer cells frequently over-express Bcl-2 and/or Bcl-xL in order to promote survival or confer resistance to chemotherapy. Inhibition of these anti-apoptotic Bcl-2 family members should specifically target the abnormal cell death pathway found in these cancer cells and offers an attractive approach to antitumor therapy.  Using structure based drug design we have discovered small molecule BH-3 mimetics that effectively antagonize the function of anti-apoptotic Bcl-2 family proteins by competing for binding to their hydrophobic surface groove. ABT-263 is an orally bioavailable inhibitor with high affinity (Ki
SIRT1 against breast cancer through downregulating Bcl-2 protein.
Authors: Dar-Ren Chen
Journal: Journal of Clinical Oncology (2012)

34 Background: SIRT1, a member of the class III histone deacetylase (HDAC) family, is the mammalian orthologue of yeast Sir2. It has been reported to play a key role in a variety of physiological processes such as genomic stability, metabolism, neurogenesis and cell survival due to its ability to deacetylate both histone and numerous non-histone substrates. The deacetylase function of SIRT1 has been suggested as playing a role in prolonging the life of mammals. However, the suggested functions of SIRT1 as a potential tumor promoter have been challenged by observations of their respective down- and up-regulation in various cancers. The aim of the present study was to simultaneously evaluate the expression levels of SIRT1 and Ki67, the index of cellular proliferation, in normal and tumor tissues of the breast from 27 breast cancer patients and to determine the role of SIRT1 in breast tumorigenesis. Methods: A total of 27 breast cancer patients were included. Tumor tissues and matched normal breast tissues were immediately frozen after collection between 2007 and 2008. Immunohistochemistry and reverse transcription-polymerase chain reaction were applied for analyses of patients’ specimens. Cell proliferation assay, cell cycle analysis and Western blotting were used to investigate the effects of sirtinol on the human breast cancer lines MCF-7 and MDA-MB-231 cells. Results: Immunohistochemistry showed that there is a high correlation between SIRT1 and Ki67 expression. In addition, our results showed that inhibition of SIRT1 induces anti-cell growth in both MCF-7 (ER-positive, non-invasive) and MDA-MB-231 (ER-negative, invasive) breast cancer cell lines, especially in MDA-MB-231 cells. The levels of pro-survival protein Bcl-2 were dramatically decreased in both breast cell lines following sirtinol treatment. Conclusions: Our present study revealed that inhibition of SIRT1 activity may be a promising chemotherapeutic strategy against breast cancer.
Thrombin Generation Measurement In Whole Blood As a Control For Vitamin K Antagonist Treatment - Effect Of Thrombomodulin
Authors: Saartje Bloemen, Marieke de Laat, Arina ten Cate-Hoek, Hugo ten Cate, Bas De Laat, H. Coenraad Hemker, Raed Al Dieri
Journal: Blood (2013)
USING A "CONVERSION FACTOR" TO ESTIMATE ADENOMA DETECTION RATE
Authors: P. T. Rajasekhar, T. J. Lee, M. D. Rutter, M. G. Bramble, D. W. Wilson, J. E. East, B. P. Saunders, A. P. S. Hungin, C. J. Rees
Journal: Gut (2012)
Chemical modifiers of cancer treatment.
Authors: C N Coleman, E A Bump, R A Kramer
Journal: Journal of Clinical Oncology (1988)

Chemical modification is a concept in cancer therapy in which the state of tumor cells or normal tissues is modified such that a therapeutic gain can be achieved using conventional therapeutic modalities. Hypoxic zones targeted as cells within them may be radiation resistant, poorly perfused by chemotherapeutic agents, and possibly drug resistant due to hypoxia-related gene amplification. Nitroimidazoles have gained particular attention as chemical modifiers because they can increase the radiation sensitivity of hypoxic cells, are cytotoxic to hypoxic cells, can increase sensitivity to chemotherapeutic agents, and are useful for imaging hypoxic cells. While both radiosensitization and chemosensitization require hypoxia, the mechanism of the enhancement of each of the modalities is different. The 2-nitroimidazole hypoxic sensitizers SR 2508 and Ro-03-8799, which are less toxic than the prototype misonidazole (Miso), are in clinical trials, and dual function molecules that include a hypoxic sensitizer and alkylating function are being developed. The presence of both acutely and chronically hypoxic cells in animal tumors has been demonstrated by new imaging techniques. Oxygen delivery to tumors is being altered by the use of perfluorocarbons, and agents that alter hemoglobin affinity for oxygen. Compounds that are selectively toxic to hypoxic cells are being developed. Nonhypoxic modifiers are also being investigated. Thiol modification, particularly the alteration of glutathione concentration, has complex effects on the cell's biochemistry, in addition to affecting the competition between oxygen and thiol groups for the restoration and fixation of radiation-induced radicals. WR-2721 is being studied as a means of reducing the normal tissue toxicity of radiation and chemotherapy. Increased thiol concentration may be a mechanism of cross-resistance between certain chemotherapeutic agents and radiation.
Willingness to be informed during treatment among cancer patients?
Authors: G. Gravis, C. Protiere, C. Tarpin, F. Viret, T. Aurran, M. Mohty, P. Viens
Journal: Journal of Clinical Oncology (2006)

18522 Background: More than ever the question of patient’s information remains a matter of debate. Some consider information as a risk of anxiety, others see it as a way of patient implication in the treatment and allowing a better patient-physician relationship. Does the model of informed, empowered patient valid in European institution? To assess the impact, in term of anxiety, quality of life (QoL) and satisfaction, of a change in usual practice by proposing a specific structured and organized file (SSOF) including all medical information in real time. Methods: To evaluate this practice change, patients (breast or colon cancer and lymphoma) who have accepted to participate have been randomized between an “access” to the SSOF arm and a “non access” arm. The patients after being randomized in the “access” arm have had the choice to hold, or not, the SSOF. To help the patient, SSOF contains a lexical and a designed trained person was available. Anxiety (state-trait anxiety scale), Qol (EORTC QLQ-C30) and satisfaction were assessed at baseline, during and at the end of the treatment. Moreover, impact of this change was also assessed among the patients’ nurse, general practitioner and referent physician in our institution. Results: Among the 277 eligible patients, only 12 (4%) have refused to participate in the study. 134 have been randomized in the “non-access” arm and 131 in the “access” arm. A counter intuitive result was that no one of these 131 patients has refused to hold the SSOF. No statistical difference in baseline scores of QoL and anxiety scores between the two arms was observed at the time of randomization. Conclusions: First observation is that when you give the opportunity to hold an extended information all patients want to benefit from, even in French European institution. No significant financial relationships to disclose.
A Randomized Phase I Trial of Melphalan + Bortezomib as Conditioning for Autologous Transplant for Myeloma: The Effect of Sequence of Administration.
Authors: Sagar Lonial, Jonathan Kaufman, Claire Torre, Amelia Langston, Mary J. Lechowicz, Christopher Flowers, Stephanie McMillan, Heather Renfroe, Leonard T Heffner, Edmund K Waller
Journal: Blood (2008)