tbuckley/cabot-search huggingface dataset:
Filgrastim prophylaxis in elderly cancer patients: A French multicenter observational study (TULIP).
Authors: Ivan Krakowski, Delphine Badinand Ep Van Den Bussche, Khaled Benabed, Daniela Burlacu, Stephane Corbinais, Rafik Diab, Amr El Weshi, Elizabeth Fabre, Miriam Gardner, Maya Hacini, Philippe Janoray, Nicolas Jovenin, Jean-Loup Mouysset, Nacera Sakek, Kamel Laribi
Journal: Journal of Clinical Oncology (2016)

e21530 Background: Neutropenia, one of the most frequent dose-limiting toxicities in cancer patients, can generate serious life-threatening complications, especially in elderly patients. Few studies are currently available among this specific subpopulation, justifying the need for better understanding of daily medical practices in terms of use of growth factors to prevent chemotherapy (CT)-induced neutropenia. Methods: Multicenter, observational, prospective cohort study conducted by 112 oncologists in cancer patients aged 65 and above, undergoing CT and initiating a prophylactic treatment with filgrastim. Patients were followed according to routine medical practice from filgrastim initiation until the end of the CT or after a maximum of 6 cycles. Results: From January 2014 to May 2015, 1119 evaluable patients were documented in the study (mean age 73.9 ± 6.2 years, 52.6 % Men). The majority was suffering from solid tumor (72.9%) with ECOG 0-1 for 79.7% of them. Among patients with identified risk of febrile neutropenia, 66% had a global risk ≥ 20%, and 34% < 20%. Through all CT cycles, no differences were observed between age classes ([65-74], [75-85] or > 85) in dose, duration and time to first injection from CT start. For 70.1% of patients filgrastim was administered during the first cycle of CT and 83.5% received primary prophylaxis (PP).The median time from CT start until filgrastim was 4 days. The median duration of filgrastim treatment was 3 and 5 days respectively for the 7 day-cycle and 14/21/28 day-cycles CT regimen. Dose reductions and delays CT were less frequent in patients receiving PP (respectively 4.8% and 7.1%) than in secondary prophylaxy (respectively 9.2% and 13.3%). Also, the frequency of chemotherapy dose reductions (5.5%) and delays (8%) was low regardless of the patient age. Conclusions: This study in elderly patients shows no difference in therapeutic care of patients according to their age group. Few CT dose reductions and delays were observed.
NHS plan is at risk from cuts to public health and social care, MPs warn
Authors: Gareth Iacobucci
Journal: BMJ (2016)

The NHS’s five year plan to transform health and care services in England is being jeopardised by cuts to public health, education and training, and social care, a new report from MPs has warned.1

The government’s 2015 spending review agreed to increase the NHS budget by an additional £8.4bn (€10bn; $11.1bn) a year above inflation by the year 2020-21 as a commitment to fund the NHS’s plans set out in its Five Year Forward View .2 3 But although previous spending reviews defined health spending as the whole of the Department of Health’s budget, the 2015 review defined it solely in terms of NHS England’s budget and excluded areas that had seen budgets cut, such as …
Abstract 4775: Astrocyte elevated gene-1(AEG-1)as a potential diagnostic/prognostic marker for prostate cancer
Authors: Radhika Gade Andavolu, Catherine Stafford, Patrick Herling, Isabella Bianco, Jean-Luc Cardenas, Henry Go, Svetlana Rubakovic, Murthy V. Andavolu
Journal: Cancer Research (2016)

Abstract AEG-1/MTDH/LYRIC was initially identified as a HIV-1-inducible gene in primary human fetal astrocytes. Astrocyte Elevated Gene-1 (AEG-1) is ubiquitously overexpressed in all or most cancers and plays a regulatory role in diverse and multiple processes of carcinogenesis. AEG1 is a multi-functional regulator of normal and abnormal physiology; it contributes to broad-spectrum resistance to various chemotherapeutics; and it was recently proposed as the first potential ‘pan-cancer’ gene However, despite its critical relevance to carcinogenesis, until now genetic polymorphisms for this important gene have not been studied for association with cancer susceptibility. For example, though studies have reported AEG-1 gene expression in animal models and tumor tissues, no studies have been reported in Caucasians on the AEG-1 gene polymorphisms in large samples to establish an association with cancers. We report a PCR-RFLP screening protocol for AEG-1 gene polymorphism which is cost effective, simple and reproducible. This study also shows the strong association of AEG-1 gene with prostate cancer risk and metastasis. DNA and RNA was isolated from 232 normal healthy age matched male Caucasians and 129 prostate cancer patients recruited in the study with an informed consent. AEG-1 gene polymorphism (rs2438211) was screened using PCR-RFLP method. Patients were compared with normal healthy controls and also within patient group comparisons were made between primary and metastasis cases. Genotype analysis was done using IBM SPSS 22 software and gene expression analysis was done using RT2 profiler PCR Array Data analysis version 3.5 (SABIOSCIENCES). A strong association of AEG-1 gene polymorphism with prostate cancer (p&amp;lt;0.0001) was observed. A high frequency of the mutant allele was observed in patients (27%) as compared to normal healthy controls (7.9%).This study also highlights the possible effect of AEG-1 interaction with other genes (p53, BCCIP) contributing to tumorigenesis. Citation Format: Radhika Gade Andavolu, Catherine Stafford, Patrick Herling, Isabella Bianco, Jean-Luc Cardenas, Henry Go, Svetlana Rubakovic, Murthy V. Andavolu. Astrocyte elevated gene-1(AEG-1)as a potential diagnostic/prognostic marker for prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4775.
Abstract 4402: Glycosyltransferase ST6Gal-I enables cancer cells to survive upon growth factor deprivation
Authors: Colleen Britain, Susan Bellis
Journal: Cancer Research (2016)

Abstract Tumor growth often outpaces the tumor's ability to form new vascularization leading to a tumor microenvironment containing areas with limited access to serum-derived growth factors (GFs). How tumor cells are able to proliferate and survive in the absence of GFs is not completely understood. Recent work from our group has uncovered a novel mechanism by which ST6Gal-I, a glycosyltransferase upregulated in many cancers, enables cells to evade GF deprivation-mediated apoptosis. ST6Gal-I is a trans-Golgi sialyltransferase that catalyzes the addition of a bulky, negatively charged sialic acid in an α2-6 manner to the termini of N-linked glycans on glycoproteins bound for the plasma membrane. This sialic acid addition can modulate protein conformation and function, similar to phosphorylation. Prior studies from our group show that ST6Gal-I activity confers a cancer stem cell phenotype as well as enhances chemoresistance, leading us to hypothesize that ST6Gal-I promotes tumor cell survival, invasion and metastasis. To better understand the role ST6Gal-I plays in tumor cell survival upon GF deprivation, we monitored the response of ovarian and pancreatic cancer cells with either ST6Gal-I overexpression or knockdown to serum starvation. Upon serum starvation, cells overexpressing ST6Gal-I preferentially survived and continued to proliferate whereas cells with ST6Gal-I knockdown underwent cell death more readily, as evidenced by live-dead cell staining and cell proliferation assays. Furthermore, in the absence of serum, ST6Gal-I activity promotes the activation and/or expression of multiple pro-survival proteins, such as Akt, p70-S6K, NFκB, and cIAP2, as well as cell cycle regulators including CyclinD2. Interestingly, upon long-term GF deprivation, immunoblotting analysis reveals a selective enrichment for ST6Gal-I in the remaining live cells providing evidence that cells with high ST6Gal-I expression selectively survive GF deficiency. Collectively these data suggest that upregulation of ST6Gal-I in tumor cells may promote cell survival in areas of the tumor microenvironment that have decreased access to a blood supply. Citation Format: Colleen Britain, Susan Bellis. Glycosyltransferase ST6Gal-I enables cancer cells to survive upon growth factor deprivation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4402.
Further Limitations of the HOSPITAL Score in US Hospitals—Reply
Authors: Jacques D. Donzé, Jeffrey L. Schnipper
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Abstract 3754: Pre-clinical studies of a highly potent folate receptor targeted DNA crosslinking agent
Authors: Joseph A. Reddy, Melissa Nelson, Theresa Johnson, Christina Dirksen, Marilynn Vetzel, Spencer Hahn, LongWu Qi, Iontcho Vlahov, Christopher Leamon
Journal: Cancer Research (2016)

Abstract Folate receptor (FR) targeted small molecule drug conjugates (SMDC) have shown promising results in early stage clinical trials with Vintafolide and EC1456. In our effort to develop FR targeted SMDCs with varying mechanisms of action, we have now built a folate conjugate of a DNA crosslinking agent based on a novel DNA-alkylating moiety. This agent was found to be extremely potent with an in vitro IC50 ∼ 100 x lower than any other folate SMDC we have created to date. Treatment of nude mice bearing FR positive human xenografts led to cures in 100% of the mice at very low doses (&amp;gt; 500 nmol/kg) and a convenient once a week schedule. The observed activity was not accompanied by any noticeable weight loss (up to 20 weeks post end of dosing) or major organ tissue degeneration. In contrast, no significant anti-tumor activity (0% CR’s) was observed in treated animals that were co-dosed with an excess of a benign folate ligand, thus demonstrating its target-specific activity. Complete responses were also observed in other FR positive drug resistant (paclitaxel and cisplatin) models. Taken together, these studies demonstrated that this SMDC with a distinct DNA reacting mechanism has significant anti-tumor growth activity and tolerability, thus lending support to future clinical development of this novel FR-targeted agent. Citation Format: Joseph A. Reddy, Melissa Nelson, Theresa Johnson, Christina Dirksen, Marilynn Vetzel, Spencer Hahn, LongWu Qi, Iontcho Vlahov, Christopher Leamon. Pre-clinical studies of a highly potent folate receptor targeted DNA crosslinking agent. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3754.
Abstract 4750: Characterization of the cytoskeletal protein MACF1 in lung cancer
Authors: Najlaa Afghani, Quincy A. Quick
Journal: Cancer Research (2016)

Abstract Genetic variation between cancer patients with the same tumor and intratumor genetic heterogeneity have broadened the complexity of factors that contribute to clinical therapeutic resistance and poor response outcomes. This has made it imperative to identity atypical expressed outliers that influence the maintenance and progression of cancers. We have identified and investigated the spectraplakin protein, Microtubule Actin Cross-Linking Factor 1 (MACF1) which functions as an actin-microfilament and microtubule crosslinker for its role in lung cancers. Genomic data generated by the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) indicate that the MACF1 gene is mutated and/or amplified in ∼15% of squamous lung cancers and 25% of lung cancers, respectively. Further examination with immunohistochemistry expression analysis revealed that MACF1 is highly expressed in several lung cancer subtypes, particularly adenocarcinomas and squamous cell carcinomas, as compared to normal lung tissue. Additionally, functional studies showed that suppression of MACF1 with RNA interference significantly impaired the reproductive capacity of these solid tumors. Taken together, MACF1 represents a unique target with genetic alterations and diagnostic biomarker potential in lung cancers, the leading cause of cancer deaths in the United States. Citation Format: Najlaa Afghani, Quincy A. Quick. Characterization of the cytoskeletal protein MACF1 in lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4750.
Relationship between age and health care utilization in patients with myelodysplastic syndrome receiving supportive care.
Authors: K. Stein, A. Powers, R. L. Knoth, M. Broder, E. Chang
Journal: Journal of Clinical Oncology (2011)

6560 Background: Myelodysplastic syndrome (MDS) is rare in people under 50. Little is known about the disease in this group, particularly among those patients who receive supportive care only. Methods: This was a descriptive cohort study using a large commercial claims database. The study included patients with an initial MDS claim (ICD-9-CM 238.72-238.75) between 2/1/2007 and 7/31/2008, who were continuously enrolled for 6 months prior to and 12 months following the index claim. Patients were excluded it they were treated with either hypomethylating agents (HMA) or thalidomide analogues (TA). Once identified, patients were stratified into two group, those aged <50 and those ≥50. Demographic variables and utilization and costs were calculated in the pre- and postindex period, respectively. Results: The study identified 1,209 patients newly diagnosed with MDS and continuously enrolled in the health plan. After excluding 76 (6.3%) who were treated with HMA/TA, the final cohort contained 1,133 patients. Of these, 221 (19.5%) were <50 and 912 (80.5%) were ≥50. In the first year after diagnosis, patients <50 had significantly fewer office visits than the older group (17.5 vs. 24.2, p<.001) but were no different in the proportion hospitalized (25.8% vs. 29.2%, respectively, p=.52) or in length of stay (7.8 vs. 9.0 days, p=.42). Mean total health care charges were $30,177 (SD $53,550, Md $9,622) for patients <50 and $31,832 (SD $63,658, Md $12,248) for those ≥ 50 (p=.69). Conclusions: Despite MDS being classified as a disease of the elderly, the results showed that among the commercially insured, 1 in 5 diagnosed with MDS was under 50. Although NCCN guidelines support HMA treatment, the vast majority received supportive care only. In addition, for both age groups, hospitalizations were common, and total healthcare costs were high but did not differ between the two groups. This suggests similar levels of diseases severity. Further studies of the characteristics of patients with early onset MDS appear warranted.
Morbidity and Mortality of Renal Dialysis: An NIH Consensus Conference Statement
Authors: Consensus Development Conference Panel.
Journal: Annals of Internal Medicine (1994)

The National Institutes of Health Consensus Development Conference on Morbidity and Mortality of Dialysis brought together experts in general medicine, nephrology, pediatrics, biostatistics, and nutrition, as well as a representative of the public, to address the following questions: 1) How does early medical intervention in predialysis patients influence morbidity/mortality? 2) What is the relationship between delivered dialysis dose and morbidity/mortality? 3) Can comorbid conditions be altered by nondialytic interventions to improve morbidity/mortality in dialysis patients? 4) How can dialysis-related complications be reduced? and 5) What are the future directions for research in dialysis? After one and a half days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the consensus panel concluded the following: 1) During the period before dialysis therapy begins, patients, including children, should be referred to a renal team to reduce the morbidity and mortality incurred during this period and during subsequent dialysis therapy; 2) the social and psychological welfare and the quality of life of the patient receiving dialysis are favorably influenced by the early and continued involvement of a multidisciplinary renal team; 3) to avoid a catastrophic onset of dialysis, attempts should be made to institute intervention before dialysis therapy begins and to appropriately initiate dialysis access; 4) quantitative methods now available to objectively evaluate the relation between the delivered dose of dialysis and patient morbidity and mortality suggest that the dose of hemodialysis and peritoneal dialysis has been suboptimal for many patients in the United States; 5) factors contributing to the underdialysis of some patients include problems with vascular and peritoneal access, nonadherence to dialysis prescription, and underprescription of the dialysis dose; 6) cardiovascular mortality accounts for approximately 50% of deaths in patients receiving dialysis, and relative risk factors such as hypertension, smoking, and chronic anemia should be treated as soon as possible after the diagnosis of chronic renal failure; 7) early detection and treatment of malnutrition contribute to the improved survival of patients receiving dialysis; and 8) until randomized, controlled trials have been completed, a delivered hemodialysis dose at least equal to a measured fractional urea clearance Kdr t/V value of 1.2 (single pool) and a delivered peritoneal dialysis dose at least equal to a measured Kpr t/V value of 1.7 (weekly) are recommended.
Abstract 675: Ninjurin1, a target of p53, modulates p53-dependent tumor suppression <i>in vivo</i>
Authors: Hee Jung Yang, Seong Jun Cho, Jin Zhang, Wensheng Yan, Xinbin Chen
Journal: Cancer Research (2016)

Abstract The nerve injury-induced protein 1 (Ninjurin1, Ninj1), a homophilic adhesion molecule, is involved in nerve regeneration, inflammation and vascular regression. Ninj1 is found to be overexpressed in human cancers including hepatocellular carcinoma and acute lymphoblastic leukemia. However, the role of Ninj1 in tumorigenesis has not been elucidated. Recently, we found that Ninj1 is transcriptionally regulated by p53, which in turn regulates p53 expression through mRNA translation. Thus, the mutual regulation between p53 and Ninj1 represents a novel loop in the p53 pathway. To examine the biological significance of the p53-Ninj1 loop, we generated and monitored 4 cohorts of mice: (i) WT, (ii) Ninj1-het, (iii) p53-null, (iv) Ninj1-het; p53-null. We found that Ninj1-het mice were highly prone to skin lesions. We also found that Ninj1 deficiency shortened the life-span but decreased the incidence of sarcoma in mice without p53. Additionally, we found that Ninj1-het; p53-null mice were prone to hydrocephalus and kidney abnormality. To examine the association of Ninj1 with mutant p53, we generated and characterized Ninj1+/-; p53 R270H/- and p53 R270H/- mice. We found that Ninj1 deficiency shortened the life-span and promoted the frequency and aggressiveness of tumors in p53 R270H/- mice. Together, we conclude that Ninj1 differently regulates the tumor susceptibility in a p53-dependent manner in vivo and that the Ninj1-p53 loop plays a pivotal role in tumor suppression and longevity. Citation Format: Hee Jung Yang, Seong Jun Cho, Jin Zhang, Wensheng Yan, Xinbin Chen. Ninjurin1, a target of p53, modulates p53-dependent tumor suppression in vivo. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 675.
What do submarines have in common with diabetes?
Authors: Ebonie Rio, Ryan Timmins, David Opar
Journal: British Journal of Sports Medicine (2016)

Well, technically nothing except that a better understanding of submarines and diabetes will help in the crusade against injury and pain. Let us explain…

Fast bowling in cricket is a huge workload not only because of the repetitive nature of the action (six consecutive deliveries in one over and multiple overs bowled in one game—up to 60!) and also the forces associated with the speed of the action. One of the challenges is the variability in workload. The editorial ( see page 962 ) outlines smart technology that departs from traditional measures of counting the balls bowled (that may differ in intensity) and uses technology to provide and quantify information about the intensity of load. This game changing wearable technology aims to assist with optimising workloads, reducing injury and ensuring fast bowling preparedness. Let us hope that the British cricket team does not get hold of this Aussie brilliance…

Interestingly, Melbourne's Billy Hulin and colleagues found that high and very-high chronic workloads may protect against match injury in elite rugby league players following shorter between match recovery periods ( see page 1008 ). This may provide a surprising opportunity to manipulate training workloads in rugby to minimise match-injury risk especially when match scheduling is outside of the control of coaches.

From elite athletes to those who may struggle to complete health promoting physical activity due to musculoskeletal pain, the systematic review by Ranger and colleagues ( see page 982 ) provides a critique …
Case 47-1968
Authors: Charles S. Davidson, Benjamin Castleman
Journal: New England Journal of Medicine (1968)

Presentation of Case First admission. A forty-two-year-old woman was admitted to the hospital because of jaundice and persistent pain in the right upper quadrant of the abdomen.For six years she had had "gas pains" intermittently. Eighteen months previously she was admitted to another hospital because of epigastric distress. An oral cholecystographic study was said to show a gallstone; at laparotomy the liver was firm, nodular and slightly enlarged, and the spleen was three to four times the normal size; the gallbladder was thickened but contained no stones; cholecystectomy was performed. Biopsy of the liver revealed postnecrotic cirrhosis; biopsy . . .
Mad2 (Mitotic Arrest Deficiency 2) Is Essential for the Synergistic Proliferation Induced by Stem Cell Factor Combined with GM-CSF in Hematopoietic Progenitor Cells, Effects Reflecting the Association of c-kit with Mad2.
Authors: Shigeki Ito, Charlie Mantel, Myung-Kwan Han, Seiji Fukuda, Yoji Ishida, Robert Benezra, Hal E. Broxmeyer
Journal: Blood (2005)