tbuckley/cabot-search huggingface dataset:
Penfluridol: An Antipsychotic Agent Suppresses Metastatic Tumor Growth in Triple-Negative Breast Cancer by Inhibiting Integrin Signaling Axis
Authors: Alok Ranjan, Parul Gupta, Sanjay K. Srivastava
Journal: Cancer Research (2015)

Abstract Metastasis of breast cancer, especially to the brain, is the major cause of mortality. The inability of anticancer agents to cross the blood-brain-barrier represents a critical challenge for successful treatment. In the current study, we investigated the antimetastatic potential of penfluridol, an antipsychotic drug frequently prescribed for schizophrenia with anticancer activity. We show that penfluridol induced apoptosis and reduced the survival of several metastatic triple-negative breast cancer (TNBC) cell lines. In addition, penfluridol treatment significantly reduced the expression of integrin α6, integrin β4, Fak, paxillin, Rac1/2/3, and ROCK1 in vitro. We further evaluated the efficacy of penfluridol in three different in vivo tumor models. We demonstrate that penfluridol administration to an orthotopic model of breast cancer suppressed tumor growth by 49%. On the other hand, penfluridol treatment inhibited the growth of metastatic brain tumors introduced by intracardiac or intracranial injection of breast cancer cells by 90% and 72%, respectively. Penfluridol-treated tumors from all three models exhibited reduced integrin β4 and increased apoptosis. Moreover, chronic administration of penfluridol failed to elicit significant toxic or behavioral side effects in mice. Taken together, our results indicate that penfluridol effectively reduces the growth of primary TNBC tumors and especially metastatic growth in the brain by inhibiting integrin signaling, and prompt further preclinical investigation into repurposing penfluridol for the treatment of metastatic TNBC. Cancer Res; 76(4); 877–90. ©2015 AACR.
Health of the nhs workforce to be reviewed Out of hours fund disappoints gps' leaders Doctors advised on advertising Gps' staff can continue to hand over medicines Trust board members must back nhs
Journal: BMJ (1997)

A partnership has been set up to review the health of the NHS workforce. The main objectives are to assess available evidence on morbidity among all grades of NHS staff;to estimate the cost of avoidable work related sickness; and to make recommendations for future action.

Under the auspices of the Nuffield Trust the partnership includes representatives of the Department of Health, the BMA, the NHS Confederation, the British Association of Medical Managers, the Faculty of Occupational Medicine, the General Medical Council, the Institute of Health Services Managers, the National Counselling Service for Sick Doctors, the Royal College of Nursing, the Royal College of Psychiatrists, and UNISON.

The project team, which expects to report in March 1998, is led by Dr Siân Williams, a locum consultant in occupational medicine at the Royal Free Hospital in London.

# Out of hours fund disappoints gps'leaders {#article-title-2}

GPs' leaders are disappointed that the out of hours development fund will not be increased in the 1998–9 financial year. They have told the Department of Health that it is unsatisfactory to provide an …
Identifying high-priority quality measures for breast cancer quality improvement using data from a nationally representative sample
Authors: M. J. Hassett, J. C. Weeks
Journal: Journal of Clinical Oncology (2009)

6507 Background: We previously developed a simple, data-based strategy for selecting high-priority quality measures, and applied it to practice performance data from eight National Comprehensive Cancer Network (NCCN) centers to identify high-priority measures for breast cancer care. We now seek to evaluate the generalizability of these results by identifying which measures rank highly when practice performance data from a nationally representative sample, rather than a select group of cancer centers, are used. Methods: Using SEER-Medicare data, we assessed practice performance for 9933 women 65–70 years old diagnosed 1998–2002 with non-metastatic invasive breast cancer. For each quality measure, we determined the number of eligible patients, the number who did not receive recommended therapy, and the overall and target (goal) concordance values. We entered these data into a previously described algorithm to derive a numerical prioritization score for each measure. Spearman correlations were used to analyze comparisons between datasets. Results: We were able to evaluate practice performance relative to most (18/30; 60%) of the measures included in our original NCCN analysis. The absence of oral hormone therapy and DCIS pathology data in SEER-Medicare precluded assessments of quality relative to the remaining measures. The highest-ranking measures recommended chemotherapy for hormone-receptor positive tumors &gt;1 cm, axillary node surgery and radiation after lumpectomy for stage I-II cancer, and no radiation after mastectomy for node-negative cancer &lt;5 cm. Excluding hormone therapy and DCIS measures, the 6 highest-ranking measures in the SEER-Medicare and NCCN analyses were identical. Correlation between the prioritization scores for the 18 measures common to both datasets was 0.74. Conclusions: While SEER-Medicare data only include patients &gt;65 and NCCN data only represent select institutions, information from both can be used to identify high-priority quality measures. That the same measures rank highly in both analyses suggests these are comprehensive, generalizable, policy ready national standards, and that this is a valid method for identifying high-priority quality measures. No significant financial relationships to disclose.
Selection of fully human anti-CD138 for detecting and therapy of multiple myeloma from combinatorial libraries and generation of novel anti-myeloma antibodies
Authors: T. Fernandez, C. Pellat-Deceunynck, S. Supiot, M. Cherel, A. Stortchevoi, R. Bataille, J.-L. Harousseau, D. B. Rubinstein, T. Guillaume
Journal: Journal of Clinical Oncology (2005)

2550 Background: Identifying cell surface antigens on tumor cells presents a challenge due to the need to preserve three-dimensional epitopic sites on the cell surface, variable expression of Ags, and stereotactic interference of closely-associated proteins on the cell surface. To date, no clinically applicable molecular target has been identified in myeloma. CD138 (Syndecan-1), a proteoglycan expressed by plasma cells represents a target for anti-myeloma antibodies. Methods: Combinatorial immunoglobulin (Ig) libraries with phage display which result in in vitro human Ig Fab fragments without the need to maintain on-going hybridoma culture were generated. A library of 1010 clones from the cDNA of peripheral blood mononuclear cells of patients with adenocarcinoma were used to identify anti-CD138 specific Ig. Results: Following removal of non-specific Fabs by exposing the Ig library to the epithelial cell line HEK, specific anti-CD138 were selected by exposing the Fab library to HEK transduced with human CD138. Six rounds of selection resulted in a panel of anti-CD138-bearing phage. The anti-CD138-bearing phages bound multiple myeloma CD138+ cell lines (U266, SBN) by ELISA analysis while phage alone did not. Sequencing the Fab VH and VL genes confirmed the heterogeneity of the panel of anti-CD138 Fabs. Conclusions: (i) the selected anti-CD138 Fabs are both highly specific and purely human, with no murine sequence. As such, they are are candidates for conjugation with radioisotope for detection and staging of myeloma, and due to the radiosensitivity of myeloma, cell-specific therapeutic agents. (ii)selection of combinatorial libraries against whole cells can generate a wide panel of novel myeloma-reactive antibodies. By pre-exposure to EBV-positive cells prior to reaction autologous myeloma, combinatorial antibody libraries can identify molecules for detection, therapy and study of the tumor biology of myeloma. No significant financial relationships to disclose.
The financial impact of providing oral and injectable anti-cancer medications at the Dallas Veterans Affairs Medical Center (DVAMC)
Authors: J. Dowell, W. Lai
Journal: Journal of Clinical Oncology (2004)

6146 Background: During the past decade, a number of oral and injectable chemotherapy/molecularly targeted drugs have been approved for use in cancer. These medications are expensive and are often not covered by insurance in the same manner as intravenous chemotherapy. This study sought to determine the number of patients referred to the Hematology/Oncology Section (HOS) of DVAMC solely to obtain their medications and to estimate the financial impact of these referrals on DVAMC. Methods: All new consults received by the HOS at DVAMC from 1/03–11/03 were reviewed. Charts were abstracted for the following information: medication requested, disease, age, and sex. Using the Federal prime vendor price list and a conservative estimate of dose and duration of use, an estimate of the annual cost of providing these medications was made. Results: 1038 new outpatient consults were reviewed. 47 (4.5%) were made solely for the DVAMC to provide medication recommended by an outside oncologist. The median age of this group was 72 years (range 50–86). 23 (89%) were male, 5 (11%) were female. Thalidomide was requested by 9 patients (19% of referrals), hydroxyurea by 6 (13%), gefitinib by 5 (11%), imatinib mesylate by 5 (11%), capecitabine by 4 (9%), erythropoietin by 3 (6%), anagrelide by 3 (6%), anastrozole by 2 (4%), and letrozole by 2 (4%). Octreotide, interferon, temozolamide, cyclophosphamide, melphalan, tretinoin, and danazol were each requested by a single patient. The estimated annual cost to DVAMC of providing these medications was $367,549.07. Given a 2003 budget for outpatient medications at DVAMC of $70,000,000, approximately 0.5% of this annual budget was utilized by only 47 patients. Conclusions: Inadequate insurance coverage of oral and injectable anti-cancer medications had a significant financial impact on DVAMC in 2003. More of these medications will be approved for use in the near future. It is imperative that a better system for insurance coverage be devised to avoid overburdening the already strapped VA system. No significant financial relationships to disclose.
Nude mice model of primary human nonseminoma germ cell tumors to study biology and resistance to cisplatin treatment
Authors: J. M. Piulats, M. Nadal, M. Martinez-Iniesta, S. Puertas, S. Gonzalez, A. Vidal, E. Condom, J. Germa-Lluch, X. Garcia Del Muro, A. Villanueva
Journal: Journal of Clinical Oncology (2009)

e16143 Testicular germ cell tumors (TGCTs) are the most common malignancy in young men. Recently, our group has reported the development of a model of human nonseminoma (NSE) after orthotopic nude mice implantation (Piulats et al, Amer Assoc Cancer Res. 2006). Pure and mix NSE anatomies were represented and they reproduce the main histological, genetic and epigenetic characteristics of paired primary tumors. Xenografts mimic distal dissemination patterns and cisplatin (CDDP) tumor behavior responses. This model has been useful for the study of antiangiogenic therapies (Piulats et al, ASCO. 2007), furthermore we want to demonstrate it is an useful tool to study the genetic mechanisms related with CDDP adquired resitance. We have generated in vivo five tumors showing increased resistance to CDDP by exposition to repetitive cycles and increasing the dose applied through different passages (1 yolk-sac; 1 choriocarcinoma; 2 embrional carcinoma; 1 mix tumor). A shortness time elipse between pasajes was observed for each tumor through CDDP treatments. To confirm increasin resistance, a parallel assay of chemotherapy response was performed between nontreated and CDDP resistant tumors. Whole genome analysis of tour xenografted tumors and their paired CDDP resistant tumor (#3 and #5 passage) were analyzed by CGH NimbeGen arrays using 60 Kb average windows. Few differential genomic changes were identified some of them were consistent across resistant tumors including gain of 9q21.11–9q33.3, 15q23–15q24.1, and 15q26.3 regions and loss of Xp22.33. In one tumour showing strong CDDP resistance compared with its sensitive counterpart it occur in absence of new genomic changes. No changes in the MSI or mutational TP53 status were observed in resisant tumors. Our data suggest that acquisition of tumor resistance to CDDP in TGCTs may proably depend of a combination of different mechanisms, including cromosomal imbalances. No significant financial relationships to disclose.
Trends in breast cancer treatment in United States from 2000 to 2011: Consequences of 2004 National Comprehensive Cancer Network (NCCN) guidelines change.
Authors: Elisabeth E. Arrojo, Alvaro Martinez, Frank A. Vicini
Journal: Journal of Clinical Oncology (2014)

69 Background: In 2004, the NCCN, changed the guidelines for the treatment of stage 1, HR+, &gt; 70 years(y) breast cancer patients, based mainly on the CALGB/RTOG trial, which showed that in these patients, the addition of radiotherapy (RT) to surgery and tamoxifen did not improve overall survival, but significantly decreased local relapse at 5 y. Methods: Retrospective analysis about trends in breast cancer treatment in USA from years 2000 to 2011, searching the National Cancer Data Base, reviewing 458.386 cases of breast cancer stage I, HR+, with special focus in patients &gt;70y. Chi square test was used. Results: Between years 2000-2011, in the group reviewed, mastectomy (MT) increased in women &lt;40y (+25%) and between 40-69y (+13%), while RT decreased in both groups (-20%, -3%). In women &gt;70y, MT decreased (-27%) progressively along these years, but radiotherapy increased until year 2003 (+3%), and begun to decrease in 2004 (-4%), with a final difference between 2003 and 2011 of -9%. In patients &gt;70 y, chemotherapy (CH) treatments, increased progressively (+3%) from year 2000 to 2011 (p&lt;0.001). Conclusions: Changes in NCCN breast cancer guidelines made in 2004, seem to have changed trends of breast cancer treatment in USA in patients &gt; 70y, stage I, HR+. Since then, less aggressive “local” treatments (-4% for MT and -9% for RT) are been performed. Despite this trend for less local therapy chemotherapy utilization has increased even though the risk of systemic disease is very low. The main risk for these patients is local failure with the associated physical, psychological and family impact as well as cost of re-staging. Local RT has demonstrated a significant reduction of this risk. Today's life expectancy for a 70 y/o woman is &gt;10y consequently local relapses and its consequences are expected. New RT techniques, such as partial breast irradiation delivered in few days are convenient and associated with very low toxicity and no mortality. Perhaps a re-look of the NCCN guidelines might be in order. [Table: see text]
Adenovirus Infections in Patients Undergoing Bone-Marrow Transplantation
Authors: Anthony F. Shields, Robert C. Hackman, Kenneth H. Fife, Lawrence Corey, Joel D. Meyers
Journal: New England Journal of Medicine (1985)

Viral infection is commonly observed after bone-marrow transplantation. We isolated adenovirus from 51 of 1051 patients undergoing marrow transplantation between 1976 and 1982. Of the 46 isolates available for typing, 13 (27.7 per cent) were of the closely related species 11, 34, or 35 (subgenus B). All 13 of the patients with these species had positive urine cultures. The species have previously been associated with the acquired immunodeficiency syndrome or with renal transplantation but are not commonly found in community surveys. Invasive infection was confirmed by biopsy or autopsy in 10 of 51 patients. Seven of the 10 had virus isolated from lung, and 4 died from pneumonia attributed to adenovirus. Two of the five patients with renal isolates had evidence of virally induced renal impairment, and both patients with liver isolates had adenovirus hepatitis. There was no common source that accounted for these adenovirus infections, and the most likely source of infection appeared to be endogenous viral reactivation. The only identifiable risk factor for the development of infection and for severe disease was the presence of moderate to severe graft versus host disease. (N Engl J Med 1985; 312:529–33.)
Abstract 108: Hemodynamic Effects of an Automatic Simultaneous Sternothoracic CPR Device in Patients with Cardiac Arrest
Authors: Kyoung Chul Cha, Hyun Kim, Dong Gun Lee, Yong Sung Cha, Oh Hyun Kim, Tae Hoon Kim, Kang Huyn Lee, Sung-oh Hwang
Journal: Circulation (2014)

An automatic simultaneous sternothoracic CPR device (X-CPR®) is an apparatus performing CPR by providing simultaneous constriction of the thorax with a thoracic strap as well as compression of the sternum with a piston in a cycle. This study was conducted to compare hemodynamic effects of CPR using X-CPR with standard manual CPR in out-of-hospital cardiac arrest (OHCA) patients. Out of 62 adult patients with non-traumatic OHCA who arrived at emergency department, 24 patients (X-CPR group) received CPR using X-CPR and 38 patients (S-CPR group) received standard CPR. Acquisition and analysis of hemodynamic data was completed in 11 patients (46%) of X-CPR group and 14 patients (37%) of S-CPR group. Peak femoral arterial pressures and right atrial pressures during compression, right atrial pressures during relaxation, and end-tidal CO2 pressures were not different between two groups. Femoral arterial pressures during relaxation and calculated coronary perfusion pressures (CPP) were higher in X-CPR group than ...
A comparison of combination docetaxel/carboplatin versus sequential docetaxel then carboplatin in patients with recurrent platinum-sensitive ovarian cancer
Authors: A. Alvarez Secord, L. J. Havrilesky, R. V. Higgins, L. R. Nycum, M. F. Kohler, L. E. Puls, R. Holloway, J. T. Soper, F. A. Valea, A. Berchuck
Journal: Journal of Clinical Oncology (2006)

5092 Background: Combination paclitaxel and platinum-based chemotherapy has been shown to improve survival in patients with recurrent platinum-sensitive ovarian cancer. However, the incidence of neurotoxicity was significantly greater with combination therapy than with other platinum-based regimens. The aim of this study was to compare the efficacy and adverse event profile of combination versus sequential weekly docetaxel and carboplatin therapy in patients with recurrent platinum-sensitive ovarian cancer. Methods: Patients with recurrent platinum-sensitive ovarian, peritoneal, or tubal cancer were randomized to either weekly docetaxel 30 mg/m 2 /days 1 and 8 and carboplatin AUC 6/day 1 q 3 weeks (regimen A) or docetaxel 30 mg/m 2 /days 1 and 8, repeated every 3 weeks for 6 cycles followed by carboplatin AUC 6/day 1 every 3 weeks (regimen B) for 6 cycles or until disease progression. The primary endpoint was time to progression (TTP). Results: At the time of this analysis, 51 patients, with a median age of 65.1 years, had been enrolled. There were 25 randomized to regimen A and 26 to regimen B from January 2004 to April 2005. There were no differences between the groups with respect to age, performance status, prior consolidation therapy, or anatomic site of cancer. The study is still open to accrual and thus far the overall response rate was 51% (2 CR, 24 PR) with stable disease in 26%. Median TTP was 12.6 months. The incidence of grade 2 or 3 neurotoxicity and grade 3 or 4 neutropenia was higher with regimen A compared to regimen B (15% vs. 3%; 44% vs. 10%), respectively. Conclusions: Combination and sequential weekly docetaxel and carboplatin have significant activity in recurrent platinum-sensitive ovarian cancer. Both regimens have a low incidence of moderate to severe neurotoxicity relative to that observed in other studies that employed paclitaxel. [Table: see text]
中国西部贫困农村孕期微营养素补充对出生体重、分娩孕周和围产儿死亡影响的研究：双盲整群随机对照试验
Authors: Lingxia, Zeng, Michael, Dibley, Yue, Cheng, Shaonong, Dang, Suying, Chang, Lingzhi, Kong, Hong, Yan, 曾令霞
Journal: BMJ (2009)

目的以单纯补充叶酸为对照，评价孕期补充多种微营养素或铁／叶酸对出生体重、分娩孕周和孕晚期血红蛋白的影响。设计采用整群随机双盲对照试验设计。地点中国陕西省的两个贫困县（长武县和彬县）。研究对象5828名孕妇及其分娩的4697名活产新生儿。干预措施以村为单位整群随机化，同一个村的孕妇孕期每天补充叶酸（对照组）、铁／叶酸或多微营养素。多微营养素含15种推荐量的维生素和矿物质。主要结局指标测量出生体重、身长、头围在产后72小时内测量。通过产后42天访视收集新生儿生存情况。结果与单纯补充叶酸比较，多微营养素可显著提高出生体重42g（95％CI7—78g）；孕期补充多微营养素和铁／叶酸均可显著增加分娩孕周（铁／叶酸：0．23周，95％CI0．10～0．36周；多微营养素：0．19周，95％CI0．06～0．32周）。铁／叶酸可显著减少34周以内的早产（RR0．50，95％CI0．27～0．94，P=0．031）。相对于纯叶酸组，多微营养素和铁／叶酸均可显著增加孕妇孕晚期的血红蛋白水平（铁／叶酸：5．0g／L，95％CI2．0～8．0g／L，P=0．001；多微营养素：6．9g／L，95％CI4．1～9．6g／L，P〈0．001）。孕期营养素补充对围产儿死亡没有明显影响，但铁／叶酸可减少54％（RR0．46，95％CI0．21～0．98）的7天内新生儿死亡。结论与对照组（叶酸）比较，在中国贫困农村孕期补充铁／叶酸可延长分娩孕周从而减少早期新生儿死亡；多微营养素可适当增加出生体重，尽管如此，对早期新生儿死亡并无明显影响。在孕期微营养素干预中，剂量充足的铁对于降低发展中国家的新生儿死亡是最关键的。
Synchronous Multiple Ossifying Tumors of the Digits
Authors: Yohei Hamade, Reine Moriuchi, Toshinari Miyauchi, Kazuhiko Hirachi, Mitsuru Yanai, Yuichiro Fukazawa, Nobuki Miyamoto, Takaya Fukumoto, Takashi Anan, Satoko Shimizu
Journal: Circulation (2016)
Impact of the 2010 Consensus Recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee
Authors: Lesley Seymour, Susan Groshen, Gary L. Rosner, Daniel M. Sullivan, David R. Spriggs, Steven Reeves, Amy Gravell, S. Percy Ivy, Mark J. Ratain
Journal: Clinical Cancer Research (2015)

Abstract Oncology phase III trials have a high failure rate, leading to high development costs. The Clinical Trials Design Task Force of the Investigational Drug Steering Committee of the NCI Cancer Therapy and Evaluation Program developed Recommendations regarding the design of phase II trials. We report here on the results of a Concordance Group review charged with documenting whether concordance rates improved after the publication of the Recommendations. One hundred and fifty-five trials were reviewed. Letter of Intents (LOI) from the post-Recommendation period were more likely to be randomized (44% vs. 34%) and biomarker selected (19% vs. 10%). Single-arm studies using time-to-event endpoints (benchmarked against historical data) were similar, as was the type of tumor. There was a significant improvement in the rate of concordance, with 74% of LOIs scored as concordant compared with 58% before the Recommendations (P = 0.042). This included a marked decrease in the use of single-arm designs to evaluate the activity of drug combinations (19% vs. 5%, P = 0.009). There were areas for which clarification was warranted, including the need for protocols to include further development plans, the use of realistic benchmarks, the careful evaluation of historical controls, and the use of a standard treatment option as a control. Ongoing critical evaluation of current trial design methodology and the development of new Guidelines when appropriate will continue to improve drug development ensuring that safe and effective cancer therapeutics are made available to our patients as quickly and efficiently as possible. Clin Cancer Res; 21(22); 5057–63. ©2015 AACR.
Flipping the model for access to patient records
Authors: Ben Adams
Journal: BMJ (2016)

Flipping the model for access to patient records NHS England would like to make it clear that care.data is a separate project to the online GP records programme.The online GP records system is an ongoing process with a defined end date of completion (2018) that will allow patients online access to their medical records from their GP practice.This programme is not running under the care.dataremit, which will be storing medical data from NHS patients on a central database managed by HSCIC and using this as a real world data tool.