tbuckley/cabot-search huggingface dataset:
Depot medroxyprogesterone and risk of breast cancer [letter]
Authors: Gray Rh
Journal: BMJ (1989)

A higher risk of breast cancer has been recorded in current or recent users of Depo-Provera and oral contraceptives (OCs) than women who have not taken steroid hormones for 5 or more years.  Given the observation that OCs protect users from both fibroadenoma and fibrocystic disease it is hypothesized that the higher risk of breast cancer among current  or recent steroid hormone acceptors may reflect an unmasking effect due to the suppression of benign breast disease by these drugs.  A malignant lump would be more easily detected in a steroid contraceptive user with suppressed benign breast disease than in a nonuser with active benign breast disease; in the latter case radiographically dense breast can mask early malignant tumors.  Support for this theory is provided by the greater incidence of benign breast disease in women under 45 years of age and the increased risk of OC-associated breast cancer only in women in this age group.  To eliminate possible early detection bias in studies of breast cancer and hormonal contraceptive use it is recommended that data on the presence and extent of benign breast disease at the time of breast cancer diagnosis be collected.
RTOG 0229: A phase II trial of neoadjuvant therapy with concurrent chemotherapy and high-dose radiotherapy (XRT) followed by resection and consolidative therapy for LA-NSCLC.
Authors: M. Suntharalingam, R. Paulus, M. J. Edelman, M. Krasna, W. Burrows, E. Gore, S. Yom, H. Choy
Journal: Journal of Clinical Oncology (2010)

7024 Background: Multimodality therapy has curative potential in stage III NSCLC. Mediastinal clearance after chemoXRT is associated with superior outcome and may serve as an intermediate marker for efficacy. RTOG 0229 evaluated induction concurrent chemo and full-dose XRT(61.2Gy) in stage III NSCLC. Methods: Pts with stage III NSCLC (pathologically proven N2 or N3) were eligible. Surgeons were required to demonstrate expertise in surgery after chemoXRT. Induction chemo and full dose XRT (CBDCA AUC =2.0, paclitaxel 50 mg/m2 q week × 6, 50.4 Gy to the mediastinum and primary tumor and boost of 10.8 Gy to gross dz). The mediastinum was reassessed prior to or at the time of resection. Pts who had not progressed received CBDCA AUC =6, paclitaxel 200 mg/m2 q 21d × 2. The primary endpoint was mediastinal nodal sterilization (MNS). Results: 60 pts were accrued, 57 were eligible. Median age: 59 , 61% M, PS =0: 77%, N2: 98% N3: 2%. Histology: 51% adeno, 19% SCC, 28% NSCLC-NOS. 95% received RT per protocol; 91% received induction chemoXRT as per protocol, 49% with dose modifications. Grade 3/4 toxicities: heme 35%, GI 14%, pulmonary 23%. 43 pts (75%) were evaluable for the primary endpoint; 36 pts underwent resection. 7 pts had residual mediastinal dz. 27/43 (63%) achieved mediastinal clearance. The primary endpoint of the study was met (improving MNS from 50 to 70% with power of 80% and significance level of 0.05). There was a 14% (5/37) incidence of grade 3 postoperative pulmonary complications. There was only one postop grade 5 toxicity (3%). Median follow-up is 20 months. Conclusions: This multi-institutional trial confirms the ability of neoadjuvant concurrent chemo and full dose XRT to sterilize known mediastinal nodal disease. The acceptable postoperative complication profile supports the contention that trimodality therapy remains a viable option for carefully selected NSCLC pts presenting with stage III disease.This project was supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422. Overall survival Progression-free survival Median (mos) (95% CI) 26.6 (18.1, not reached) 13.1 (8.0, 18.9) 1-year rate (95% CI) 77% (64, 86) 52% (38, 64) No significant financial relationships to disclose.
P0708 : S-adenosylmethionine (SAM) enhances antioxidant enzyme systems, glutathione biosynthesis and switches MAT2/MAT1 turnover in hepatitis c virus expressing cells
Authors: S.A. Lozano Sepúlveda, E. Bautista Osorio, P. Cordero Pérez, L.E. Muñoz Espinosa, M.C. Gutiérrez Ruiz, A.M. Rivas Estilla
Journal: Journal of Hepatology (2015)
Abstract 855: Circulating Mesoangioblasts Differentiate Into Cardiac Myocytes And Improve Function After Acute Myocardial Infarction
Authors: Masayoshi Iwasaki, Masamichi Koyanagi, Stefan Rapp, Corina Schuetz, Philipp Bushoven, Dietmar Schranz, Beatriz G Galvez, Giulio Cossu, Andreas M Zeiher, Carmen Urbich, Stefanie Dimmeler
Journal: Circulation (2007)

Mesoangioblasts (MAB) are vessel-associated cells identified during embryonic development. In contrast to hemangioblasts, MAB express mesenchymal (CD73) and endothelial marker, but lack the hematopoietic marker CD45. We recently identified circulating MAB in children. Children-derived MAB showed vigorous proliferation capacity and high telomerase activity. However, the potential of cardiac differentiation in these cells was not elucidated. Therefore, we tested the capacity of children-derived MAB to aquire a cardiomyogenic phenotype. MAB expressed several cardiac transcription factors such as Nkx2.5, GATA4 and MEF2C and the stem cell markers c-kit and islet-1. In order to assess cardiac differentiation capacity, we performed co-culture assays with neonatal rat cardiomyocytes (CM). Immunochemical analysis revealed that MAB expressed cardiac α-sarcomeric actinin 6 days after co-culture. Moreover, human troponin T (TnT) was expressed as demonstrated by human specific RT-PCR. To confirm these data, we examined TnT expression in MAB isolated of a 2 years old patient with a known mutation of TnT. Sequences of the cloned RT-PCR products were identical to human TnT except for the known mutation providing genetic proof of concept for cardiac differentiation. In order to exclude fusion between MAB and CM as a mechanism, we used paraformaldehyde-fixed CM as scaffold. In this assay, human TnT also was detected, indicating that differentiation is sufficient to induce cardiac marker gene expression. Next, we tested the effect of MAB to improve cardiac function. MAB were injected intramuscularly in nude mice after myocardial infarction. Functional analysis using Millar catheter 2 weeks after infarction demonstrated that cell therapy lowered filling pressure and preserved diastolic function when compared to the PBS injected group (LVEDP: −20.3%, tau: −20.6%, vs PBS injected heart). Furthermore, left ventricular volume was also decreased (LVEDV/weight −27.3%). In summary, children-derived MAB express cardiac-specific genes after co-culture with CM and improved cardiac function in vivo. Given that MAB can be easily isolated and expanded from peripheral blood, these cells might be suitable to augment cardiac repair in children with heart failure.
Cisplatin (Cis)/etoposide (VP16) compared to cis/irinotecan (CPT11) in extensive-stage small cell lung cancer (E-SCLC): Pharmacogenomic (PG) and comparative toxicity analysis of JCOG 9511 and SWOG 0124
Authors: P. Lara, M. Redman, H. Lenz, M. Gordon, T. Shibata, H. Fukuda, T. Tamura, N. Saijo, R. Natale, D. Gandara
Journal: Journal of Clinical Oncology (2007)

7524 Introduction: J9511 demonstrated a significant survival benefit for Cis/CPT11 over Cis/VP16 in Japanese patients (pts) with E-SCLC (Noda, et al. NEJM 2002). S0124 is the confirmatory North American phase III trial (accrual completed) using the identical J9511 protocol. We hypothesized that toxicities would differ between North American &amp; Japanese pts due in part to differences in the distribution of genetic polymorphisms involved in chemotherapy metabolism. Methods: Toxicity data were compared among 706 pts enrolled in J9511 &amp; S0124 receiving common treatment using a logistic model adjusted for age, sex, and performance status (PS). Select polymorphisms of the UGT1A1, ABCB1, &amp; OATP genes in genomic DNA were evaluated in 142 pts in S0124 only (67 Cis/CPT11; 75 Cis/VP16). Associations between toxicity &amp; genotype within each arm were assessed using logistic regression. Results: Pt demographics for J9511 &amp; S0124 respectively: Mean age − 61 &amp; 62 years; Male sex − 131 (86%) &amp; 315 (57%); PS 0 − 19 (13%) &amp; 173 (31%); PS&gt;0 − 133 (87%) &amp; 372 (68%). Comparative toxicities (≥ grade 3) are summarized ( table ). PG analysis in S0124 pts: ABCB1 (C3435T) T/T was associated with an increased risk of CPT11 grade 3+ diarrhea (p=0.04) versus C/C and C/T. UGT1A1 (G3156A) A/A was associated with increased risk of CPT11 neutropenia (p=0.009) &amp; leukopenia (p=0.05). UGT1A1*28 TA7, typically associated with increased CPT11 toxicity, was seen in only 4 pts (2 Cis/CPT11; 2 Cis/VP16); thus no correlation was done. No gene tested was associated with VP16 toxicity. Conclusions: Significant differences in treatment-related myelosuppression exist between J9511 and S0124 pt populations. Certain polymorphisms in genes involved in CPT11 metabolism are significantly associated with CPT11 toxicities in S0124. Additional analyses are ongoing. These results support the hypothesis that toxicities may be associated with distribution of genetic polymorphisms. No significant financial relationships to disclose. [Table: see text]
Phase I/II study of targeted gene delivery in vivo—intravenous infusions of Rexin-G—demonstrate significant biologic activity by FDG PET-CT without toxicity in patients with progressive chemo-resistant sarcoma, breast cancer and pancreatic cancer
Authors: S. P. Chawla, V. S. Chua, V. Mohan, K. Alzwahereh, A. Kalra, D. Quon, E. M. Gordon, F. L. Hall
Journal: Journal of Clinical Oncology (2008)

14509 Background: Rexin-G is the first and so far only targeted gene delivery system that has been tested in the clinic (Nature Reviews/Genetics, Vol.8, p.573, 2007). Rexin-G is a pathotropic (disease-seeking) nanoparticle bearing a cytocidal cyclin G1 gene, that when injected intravenously, seeks out and accumulates in cancerous lesions, thus, enhancing local concentrations within the tumors. The purpose of the Phase I/II studies is to evaluate the safety and potential efficacy of repeated intravenous infusions of Rexin-G in patients with rapidly progressive chemo-resistant sarcoma, breast cancer, and pancreatic cancer. Methods: In these Phase I/II open label studies, patients with all types of sarcoma, or carcinoma of the breast or pancreas, were treated with 1×10e11 cfu Rexin-G, administered i.v. over 5 minutes, 2 times a week for 4 weeks (Cumulative Dose = 8×10e11 cfu) followed by a 2-week rest period. Patients with Grade 1 or less toxicity were given a dose-escalation consisting of additional treatment cycles of 1×10e11 cfu three times a week (Cumulative Dose per cycle: 1.2×10e12 cfu). Results: Aggregate analysis showed that ten of 12 (83%) evaluable patients had SD at 4–6 weeks evaluation using RECIST, while 4 of 12 (33%) and 8 of 12 (67%) had a PR or SD respectively using International PET criteria, and 5 of 12 (42%) and 6 of 12 (50%) had a PR or SD respectively using CHOI criteria. Further, the CA19–9 levels were significantly reduced in 2 of 4 of patients with pancreatic cancer. Two patients with sarcoma underwent partial resection and showed 50–95% tumor necrosis. At 5-months follow-up, the median progression-free survival and the median over-all survival was >3 months for all cancer types. Conclusions: These studies indicate (i) that repeated infusions of Rexin-G are safe and well-tolerated at these dose levels, and (ii) that Rexin-G retards tumor growth, induces significant tumor necrosis, reduces tumor density, FDG uptake, and tumor marker activity in patients with rapidly progressive chemo- resistant sarcoma, breast cancer and pancreatic cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Epeius Biotechnologies Corporation Epeius Biotechnologies Corporation Epeius Biotechnologies Corporation
Cover arrangements for consultants on leave: An analysis of job descriptions
Authors: Claire Pearson, Camilla M Janssen, M H Lewis, R B Galland
Journal: Journal of the Royal Society of Medicine (2001)

There is much ambiguity about consultant leave allowances and arrangements for cover in the National Health Service. We analysed job descriptions for 47 consultant posts advertised in mid-2000. 35 defined a duty rota but only 3 mentioned specific available leave (all different). In 32 there was no mention of cover for colleagues on leave. When a consultant is absent, colleagues tend to provide cover for emergency cases but not for elective admissions, which are managed largely by junior doctors. This arrangement is particularly hazardous in surgical specialties. If elective surgery is to continue when the consultant is absent, arrangements for leave and cover need to be more clearly defined.
The intersection of cancer, cancer stem cells, and the immune system: therapeutic opportunities
Authors: Daniel J. Silver, Maksim Sinyuk, Michael A. Vogelbaum, Manmeet S. Ahluwalia, Justin D. Lathia
Journal: Neuro-Oncology (2015)

During brain neoplasia, malignant cells subjugate the immune system to provide an environment that favors tumor growth. These mechanisms capitalize on tumor-promoting functions of various immune cell types and typically result in suppression of tumor immune rejection. Immunotherapy efforts are underway to disrupt these mechanisms and turn the immune system against developing tumors. While many of these therapies are already in early-stage clinical trials, understanding how these therapies impact various tumor cell populations, including self-renewing cancer stem cells, may help to predict their efficacy and clarify their mechanisms of action. Moreover, interrogating the biology of glioma cell, cancer stem cell, and immune cell interactions may provide additional therapeutic targets to leverage against disease progression. In this review, we begin by highlighting a series of investigations into immune cell-mediated tumor promotion that do not parse the tumor into stem and non-stem components. We then take a closer look at the immune-suppressive mechanisms derived specifically from cancer stem cell interactions with the immune system and end with an update on immunotherapy and cancer stem cell-directed clinical trials in glioblastoma.
Phase Ii, Multicenter, Open-Label, Proof of Concept Study of Tasquinimod in Patients with Advanced Hepatocellular (Hcc), Ovarian (Oc), Renal Cell (Rcc) and Gastric (Gc) Carcinomas
Authors: A.M. Oza, R. Plummer, I.B. Vergote, F. Thistlethwaite, G.A. Bjarnason, R.J. Jones, H. Mackay, E. Van Cutsem, S. Faivre, C. Descot, N. Germann, B. Escudier
Journal: Annals of Oncology (2014)
PALOMA3: A double-blind, phase III trial of fulvestrant with or without palbociclib in pre- and post-menopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer that progressed on prior endocrine therapy.
Authors: Nicholas C. Turner, Jungsil Ro, Fabrice Andre, Sherene Loi, Sunil Verma, Hiroji Iwata, Nadia Harbeck, Sibylle Loibl, Cynthia Huang Bartlett, Ke Zhang, Carla Giorgetti, Sophia Randolph, Maria Koehler, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2015)

LBA502 Background: The growth of hormone receptor (HR) positive breast cancer (BC) is dependent on the cyclin dependent kinases CDK4/6, that promote G1-S phase cell cycle progression. Resistance to endocrine treatment remains a major clinical problem for patients with hormone receptor positive breast cancer. The PALOMA3 study assessed the efficacy of palbociclib and fulvestrant in endocrine-resistant advanced breast cancer. Methods: In this double-blind phase 3 study women with HR positive/HER2 negative advanced metastatic BC whose cancer had relapsed or progressed on prior endocrine therapy, were randomized 2:1 to palbociclib (Palbo, 125 mg/d orally for 3 wk followed by 1 wk off) and fulvestrant (F, 500 mg per standard of care) or placebo (PLB) and F. Pre- and peri-menopausal women also received goserelin. One previous line of chemotherapy for metastatic disease was permitted. The primary endpoint was investigator assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), response assessment, patient-reported outcomes, and safety and tolerability. A pre-planned interim analysis was performed after 195 PFS events by an independent data monitoring committee. Results: 521 pts were randomized, 347 to receive Palbo+F and 174 to PLB+F. Baseline characteristics were well balanced. The median age was 57 and 56 years, 79% were post-menopausal, 60% had visceral disease, and 79% were sensitive to prior endocrine therapy. Prior therapy included chemotherapy for advanced disease in 33% of pts. At the time of the interim analysis the study met the primary endpoint, median PFS was 9.2 months for Palbo+F and 3.8 months for PLB+F (HR 0.422, 95% CI 0.318 to 0.560, P&lt;0.000001). Consistent benefit from Palbo was seen in pre- and post-menopausal women. The most common adverse effects Palbo+F versus PLB+F were neutropenia (78.8% vs. 3.5%), leucopenia (45.5% vs. 4.1%), and fatigue (38.0% vs. 26.7%). Febrile neutropenia was reported in 0.6% pts on Palbo+F and 0.6% pts on PLB+F. The discontinuation rate due to adverse events was 2.0% on Palbo and 1.7% on PLB. Conclusions: Palbociclib combined with fulvestrant improved progression free survival in hormone receptor positive advanced breast cancer that had progressed on prior endocrine therapy, and can be considered as a treatment option for these patients. Clinical trial information: NCT01942135.
Bundled Payments for Surgical Colectomy Among Medicare Enrollees
Authors: Faiz Gani, Martin A. Makary, Elizabeth C. Wick, Jonathan E. Efron, Sandy H. Fang, Bashar Safar, John Hundt, Timothy M. Pawlik
Journal: JAMA Surgery (2016)

The Bundled Payments for Care Improvement Initiative was proposed by the Centers for Medicare and Medicaid Services to obtain and reward a greater value of care. Still in its infancy, little is known regarding the potential effects of the Bundled Payments for Care Improvement Initiative on hospital payments and net margins.To investigate the potential effects of the Bundled Payments for Care Improvement Initiative on net margins among Medicare patients undergoing colectomy at a tertiary care hospital.Cross-sectional retrospective analysis conducted in October 2015. Medicare enrollees undergoing an elective colectomy at a large tertiary care hospital between January 1, 2009, and December 31, 2013, were identified using diagnosis-related group and International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes.Multivariable linear regression analysis was performed to calculate risk-adjusted, diagnosis-related group-specific hospital costs and payments for each patient. Net margins were calculated as the difference between total hospital costs and total payments received.A total of 821 Medicare enrollees underwent an elective colectomy and met inclusion criteria. The median age of patients was 69 years (interquartile range [IQR], 65-74 years), with 51.3% being female. Postoperative complications were observed among 27.5% of patients (n = 226) and the median length of stay was 8 days (IQR, 5-14 days). The median risk-adjusted cost among all patients was $24 951 (IQR, $16 197-$38 922). Risk-adjusted costs were higher among patients who developed a postoperative complication ($42 537 [IQR, $28 918-$72 316] vs $22 829 [IQR, $14 820-$26 150]; P < .001) and among patients with an observed to expected length of stay greater than 1 ($36 826 [IQR, $24 951-$65 016] vs $16 197 [IQR, $14 182-$23 998]; P < .001). The median payment under the fee-for-service structure was $29 603 (IQR, $17 742-$44 819), resulting in an overall net margin of $3177 (IQR, -$1692 to $10 773), with 33.7% of patients (n = 277) contributing to an overall negative margin. In contrast, under the bundled payment paradigm, the net margin per patient was $3442 (IQR, -$9311 to $8203), with 41.7% of patients (n = 342) contributing to a net negative margin.Postoperative complications, length of stay, and total hospital costs were strongly associated with hospital costs. Payments under the bundled payments system were lower and the proportion of patients contributing to a net negative margin increased. Further study is warranted to define the effect of bundled payments on quality of care and hospital finances.
Mechanosensing regulates virulence in<i>Escherichia coli</i>O157:H7
Authors: Md. Shahidul Islam, Anne Marie Krachler
Journal: Gut Microbes (2016)

Enterohemorrhagic Escherichia coli O157:H7 is a food-borne pathogen transmitted via the fecal-oral route, and can cause bloody diarrhea and hemolytic uremic syndrome (HUS) in the human host. Although a range of colonization factors, Shiga toxins and a type III secretion system (T3SS) all contribute to disease development, the locus of enterocyte effacement (LEE) encoded T3SS is responsible for the formation of lesions in the intestinal tract. While a variety of chemical cues in the host environment are known to up-regulate LEE expression, we recently demonstrated that changes in physical forces at the site of attachment are required for localized, full induction of the system and thus spatial regulation of virulence in the intestinal tract. Here, we discuss our findings in the light of other recent studies describing mechanosensing of the host and force-dependent induction of virulence mechanisms. We discuss potential mechanisms of mechanosensing and mechanotransduction, and the level of conservation across bacterial species.
Impact of erythropoietin treatment on cognitive status in anaemic patients under chemotherapy: A prospective analysis
Authors: F. Scotte, C. Ebenezer, M. Faye, N. Pelicier, S. Consoli, S. Marsan, A. Cassar-Queudeville, S. Oudard
Journal: Journal of Clinical Oncology (2008)

20625 Background: Cognitive impairment is now a known side effect of chemotherapy and can persist long time after treatment. Anaemia is one factor of cognitive dysfunction. Erythropoietins improve anaemia, quality of life and may have receptors on neuronal cells. We aimed to study the impact of erythropoietin-beta (EPO) on cognitive status in anaemic patients under chemotherapy. Methods: 35 patients (pts) diagnosed with cancer completed cognitive battery at baseline (T1), and were tested 3 months (T2) and 6 months (T3) after initiation of EPO treatment for chemotherapy induced anaemia. Primary objective was to verify the non-degradation of cognitive functions under EPO treatment according to the guidelines at T2 and T3. Attention tests (At), Grober and Buschke-B memory tests (M) and quality of life questionnaire QLQ-C30 (QOL) were used in this prospective study. Student and Wilcoxon tests were used for the statistic analysis. Results: Currently 27 pts have completed the T2 and 19 pts the T3 observations. Mean age was 54.6 (36–70) years, baseline haemoglobin (Hb) was 10.9 (8.9–11.9), T2 Hb was 12.0 (10–15.2), T3 Hb was 12.8 (10.4–15.2) g/dl. 12% of patients received neoadjuvant, 44% adjuvant and 44% metastatic therapy (n=35). All patients presented cognitive impairment at baseline. Compared to baseline no further degradation of cognitive functions was observed at T2 and T3, but an improvement was observed for At (p<0.001) and M (p=0.02) at T2. All scores for At and M were significantly improved (p<0.001) at T3. Global and cognitive QOL were improved at T3 (p=0.02 and p=0.01 respectively). Conclusions: The results indicate that EPO treatment, following the guidelines, was associated with statistically significant improvement of cognitive status in patients treated with chemotherapy. Final results will be presented. No significant financial relationships to disclose.