tbuckley/cabot-search huggingface dataset:
Effects of exercise on cancer-related fatigue and muscular strength in patients with breast cancer.
Authors: Po-Ju Lin, Kah Poh Loh, Julia Ellen Inglis, Richard Francis Dunne, Ian Kleckner, Chunkit Fung, Nikesha Gilmore, Gilberto Lopez, Charles E. Heckler, Eva Culakova, Luke Joseph Peppone, Michelle Christine Janelsins, Charles Stewart Kamen, Karen Michelle Mustian
Journal: Journal of Clinical Oncology (2019)

11507 Background: Cancer-related fatigue (CRF) is a persistent daily lack of energy commonly experienced by breast cancer (BC) patients. Due to CRF, BC patients have difficulties carrying out daily activities, become less active and consequently reduce muscular strength. Exercise can improve muscular strength and increase energy level; therefore it may alleviate CRF. This phase II RCT assessed the effects of exercise on CRF and muscular strength in BC patients. Methods: Ninety BC patients (55.5±9.6 years, 79% white, 48% and 46% under radiation or hormone therapy) were randomized into two arms: a 6-week Exercise for Cancer Patients (EXCAP) program or standard care (Control). EXCAP is a home-based, personalized, progressive exercise program combining aerobic walking and resistance band training. The Brief Fatigue Inventory was used to assess CRF and CRF interference with daily activities and a 7-10 repetition maximum chest press and leg extension strength test was used to assess upper- and lower-body strength at pre- and post-intervention. T-tests and ANCOVA with pre-intervention as the covariate were used to analyze within- and between-group changes, respectively. Results: Participants in the EXCAP group decreased CRF (-0.9±0.3, p = 0.01) and CRF interference with daily activities (-1.1±0.3, p &lt; 0.01) from pre- to post-intervention while participants in the Control group did not. The mean improvement (from pre- to post-intervention) in CRF and CRF interference of daily activities for the EXCAP group were significantly higher than the change in the Control group (both p &lt; 0.01). Participants in the EXCAP group increased upper- (3.9±1.4, p &lt; 0.01) and lower-body strength (6.4±1.3, p &lt; 0.01) from pre- to post-intervention, while participants in the Control group did not. The mean increase (from pre- to post-intervention) in lower-body strength for the EXCAP group was significantly higher than the change in the Control group (p = 0.01). Conclusions: Exercise combining aerobic walking and resistance band training reduces CRF and CRF interference with daily activities and improves muscular strength in BC patients. Results from this study provide further evidence of the benefits of exercise for supportive cancer care. Clinical trial information: NCT00851812.
MAPK regulation of SWI/SNF mediates ERα down-regulation
Authors: Jill Bayliss, David Reisman, Dorraya El-Ashry
Journal: Cancer Research (2008)

5437  Background: Estrogen receptor alpha (ERα) is a key prognostic and predictive factor in breast cancer. ERα- tumors tend to exhibit overexpression/amplification/hyperactivation of the erbB family which leads to increased downstream signaling including hyperactivation of mitogen-activated protein kinase (MAPK). We have previously shown, first in cell line models that mimic this elevated growth factor signaling by EGFR and erbB-2 in MCF-7 breast cancer cells and more recently in ERα- breast cancer cell lines and tumors, that hyperactivation of downstream p42/44 MAPK results in the reversible loss of ERα expression. A hyperactive MAPK gene profile from these cell line models which accurately predicts ERα- breast cancer further demonstrates the link between hyperactive MAPK and the ERα- phenotype. One of the genes signficantly down-regulated in these hyperactive MAPK cells was Baf57, a subunit of the SWI/SNF chromatin remodeling complex. Baf57 is the SWI/SNF subunit shown to interact with ERα and regulate its transcriptional activity.  Objective: In this study, we set out to ascertain the role of Baf57 in the MAPK mediated down-regulation of ERα expression.  Results: siRNA knockdown of Baf57 levels in MCF-7 cells not only inhibited ER activity and estrogen-induced growth as had been shown by others, but it dramatically caused the loss of ERα protein expression. The down-regulation of Baf57 protein was confirmed in the hyperactive MAPK cell line models. Indeed, Baf57 expression was substantially decreased in MCF-7 cells expressing constitutively active forms of erbB-2 or Raf-1 as well as in cells overexpressing EGFR and induced by EGF. Inhibition of hyperactive MAPK in these cell lines, restored Baf57 levels. Baf57 does not have a MAPK phosphorylation site, suggesting this was an indirect effect. But Baf155, another SWI/SNF subunit does have a MAPK site and Baf155 regulates the stability and expression of Baf57. An examination of Baf155 levels in the hyperactive MAPK cells indicated that it too was down-regulated and inhibition of MAPK restored its expression levels. Finally, re-introduction of Baf57 in the hyperactive MAPK cell lines resulted in increased ERα expression suggesting a mechanististic link between Baf57 and ERα expression.  Conclusions: MAPK mediated down-regulation of ERα is mediated in part by regulation of Baf155 and Baf57. Loss of Baf57 expression causes loss of ERα expression. We have identified a new role for Baf57 in the regulation of ERα in breast cancer and have uncovered one mechanism by which MAPK causes loss of ERα expression to result in the ERα- phenotype.
The distribution of chromosomal and microsatellite instability in colorectal cancers related to inflammatory bowel disease.
Authors: Stephan Brackmann, Maria Pretorius, Pasquale Klepp, Ole Petter Fraas Clausen, Solveig Norheim Andersen, Morten H Vatn, Ragnhild Lothe, Guro E Lind, Haavard E Danielsen
Journal: Journal of Clinical Oncology (2013)

3607 Background: Surveillance for colorectal cancer (CRC) in inflammatory bowel disease (IBD) has so far not been effective. Mucosal or fecal biomarkers may be useful in the selection of high risk patients. The yield may depend on the underlying carcinogenic pathway. In IBD associated CRC (IBD-CRC) the distribution of chromosomal instability (CIN) and microsatellite instability (MSI) is not well documented. Our objective was to determine the distribution of CIN and MSI and the association to clinico-histological factors in a cohort of patients with IBD-CRC. Methods: Ploidy was measured by high-resolution image cytometry and MSI by using two markers (BAT 25 and BAT26) in 62 patients with 72 CRC-IBD selected by matching the Norwegian Cancer Registry with IBD cohorts of three university hospitals in Oslo. The association between ploidy/MSI status and clinicohistological factors were analyzed by non-parametric tests. Results: Ploidy status was analyzed in 67 (93%), microsatellite stability in 68 (94%) tumors. Fourty-nine (73.1%) were non-diploid (43 aneuploid, 1 polyploid, 5 tetraploid), 13 (19.4 %) diploid, five (7.5%) indeterminate. Forty-three (63.2%) were microsatellite stable (MSS), four (5.8%) microsatellite instable (MSI). One tumor was MSI in BAT25 but MSS in BAT26. Twenty (29.5%) tumors showed no PCR-product in at least one of the markers. In 46 tumors, both ploidy and MSI status were available. All non-diploid tumours (36, 78.3%) were MSS and all MSI tumors (4, 8.7%) were diploid. Six (13%) tumors were diploid and MSS. Four patients were treated with 5-ASA prior to diagnosis of CRC. Three developed diploid, one aneuploid cancers. Of the untreated patients, 31 developed aneuploid, 7 diploid cancers (p=0.036). We did not find an association between age, gender, type of IBD, duration of IBD, localisation of CRC,TNM-stage and CIN or MSI. Conclusions: The majority of CRC-IBD in our cohort seem to present CIN and only a minority MSI. Some CRC-IBD patients present neither CIN nor MSI. Future studies should determine whether these display the CpG island methylator phenotype. Biomarkers for CRC-IBD should be derived from all three pathways.
Assessment of Out-of-Network Billing for Privately Insured Patients Receiving Care in In-Network Hospitals
Authors: Eric C. Sun, Michelle M. Mello, Jasmin Moshfegh, Laurence C. Baker
Journal: JAMA Internal Medicine (2019)

Although surprise medical bills are receiving considerable attention from lawmakers and the news media, to date there has been little systematic study of the incidence and financial consequences of out-of-network billing.To examine out-of-network billing among privately insured patients with an inpatient admission or emergency department (ED) visit at in-network hospitals.A retrospective analysis using data from the Clinformatics Data Mart database (Optum), which includes health insurance claims for individuals from all 50 US states receiving private health insurance from a large commercial insurer was conducted of all inpatient admissions (n = 5 457 981) and ED visits (n = 13 579 006) at in-network hospitals between January 1, 2010, and December 31, 2016. Data were collected and analyzed in March 2019.Receipt of a bill for care from at least 1 out-of-network physician or medical transport service associated with patient admission or ED visit.The incidence of out-of-network billing and the potential amount of patients' financial liability associated with out-of-network bills from the admission or visit.Of 5 457 981 inpatient admissions and 13 579 006 ED admissions between 2010 and 2016, the percentage of ED visits with an out-of-network bill increased from 32.3% to 42.8% (P < .001) during the study period, and the mean (SD) potential financial responsibility for these bills increased from $220 ($420) to $628 ($865) (P < .001; all dollar values in 2018 US$). Similarly, the percentage of inpatient admissions with an out-of-network bill increased from 26.3% to 42.0% (P < .001), and the mean (SD) potential financial responsibility increased from $804 ($2456) to $2040 ($4967) (P < .001).Out-of-network billing appears to have become common for privately insured patients even when they seek treatment at in-network hospitals. The mean amounts billed appear to be sufficiently large that they may create financial strain for a substantial proportion of patients.
Protein expression of DNA damage checkpoint in oral cancer
Authors: Yohko Kohno, Masafumi Takimoto, Eisuke Shiozawa, Hidekazu Ota
Journal: Cancer Research (2008)

1856  Background and objective: Damage and abnormality of DNA genome is the starting point of the process of malignant transformation of a normal cell. Once DNA damage occurs, eukaryotic cells can activate cell cycle checkpoints, apoptosis or senescence. Some kinases are related to cell cycle checkpoint, apoptosis and senescence pathways, and stimulate and activate other kinases. p53, a transcriptional factor mutated in over 50% of human cancers, is phosphorylated at Ser15 and Ser37 by ATM/ATR and DNA-PK. This phosphorylation promotes the accumulation and functional activation of p53 in response to DNA damage. Active Chk1 and Chk2 can phosphorylate p53 at several serine sites, enhancing its tetramerization, stability and activity. In 60% of oral cancer, p53 is mutated. It seems that some kinds of oral cancer have different signal transmission pathways which are regarded as conventional DNA damage signal transmission pathways. We used several kinds of oral squamous carcinoma cell lines to check the expression of p53 first. After treatment with genotoxic stress to culture cells, we examined the expression of each protein in DNA damage checkpoint by Western blot analysis, and checked the localization in oral mucosal tissues by immunohistochemistry. Methods: We used several kinds of oral cancer cell lines for Western blot analysis, oral mucosal tissues for immunohistochemistry and Actinomycin D for chemical induction. Antibodies were used for detecting the protein expression. Conclusion and Discussion: After DNA damage in the oral cancer cell lines, ATM kinase is activated, and Chk1 and Chk2 are phosphorylated. As for Chk2, the Thr68 site is phosphorylated after the DNA damage generally. In HSC3 cell lines, DNA-PK was degradated after DNA damage and Chk2 was phosphorylated in the Ser19 and Thr68 sites. We found out the expression of p-p53 could not be confirmed in HSC3 cells. In HSC4 cell lines, phospholylation of p53 on the Ser15 and Ser20 sites was confirmed. In HSC3 cells, the transmission system does not go through p53; Ser15 and Ser20 of p53 are not phosphorylated. In oral tissues, the expression of p-Chk2 in epithelial dysplasia was slightly stronger than in cancer tissues and localization of p53 and p-p53 was strongly seen in cancer tissues by immunohistochemical analysis. These results suggest that expression of Chk2 has an influence on that of p53 in oral cancer.
Surgical Hot Spotting
Authors: Karan R. Chhabra, Amir A. Ghaferi, Hari Nathan
Journal: JAMA Surgery (2019)

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 Surgery 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 Surgery journal
The UK Government must help end Scotland's drug-related death crisis
Authors: James Nicholls, Shirley Cramer, Steve Ryder, Deborah Gold, Saket Priyadarshi, Susanne Millar, Carole Hunter, Ron Hogg, Arfon Jones, Fiona Measham, Alex Stevens, Ian Hamilton, Iain McPhee, Niamh Eastwood, Martin Powell
Journal: The Lancet Psychiatry (2019)
Abstract #1989: Down-regulation of Neuropilin-2 suppresses in vivo growth of gastric cancer and sensitizes cells to 5FU-induced apoptosis
Authors: Shaija Samuel, Puja Gaur, Michael Gray, Ling Xia, Fan Fan, Nikolaos Dallas, Debashish Bose, Lee Ellis
Journal: Cancer Research (2009)

Introduction. The overall survival of patients with gastric cancer (GC) remains poor. Better understanding of the molecular events in GC growth may contribute toward identifying novel therapeutic targets. Neuropilin-2 (NRP-2) is traditionally known function as a non-signaling co-receptor for class 3 semaphorins and members of the vascular endothelial growth factor (VEGF) family. However, our laboratory and others have shown that tumor cell derived NRP-2 plays a role in tumor growth. We hypothesized that NRP-2 expression may contribute to growth of GC. Methods. NRP-2 expression in surgically resected GCs was assessed by immunohistochemistry. TMK-1 human GC cells were stably transfected with shRNA targeting NRP-2 and expression of NRP-2 and other signaling intermediates were analyzed by immunoblotting. Migration and invasion were determined using modified Boyden chamber assay. Metastasis gene expression profile was studied by cDNA microarray analysis. Apoptosis was determined by Annexin V/PI staining followed by flow cytometry. Tumor growth was analyzed in mice (groups of 10) injected in the liver with control and shRNA-NRP-2 expressing TMK cells. Results. In clinical GC specimens, NRP-2 expression was higher in tumor tissue than in adjacent normal mucosa. shRNA to NRP-2 effectively decreased expression of NRP-2 in TMK-1 cells without effecting NRP-1 or VEGFR-1 levels. Knock-down of NRP-2 expression led to decreased migration and invasion in vitro (p  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1989.
ROS‐Responsive Blended Nanoparticles: Cascade‐Amplifying Synergistic Effects of Sonochemotherapy with On‐demand Boosted Drug Release During SDT Process
Authors: Pengying Wu, Wei Dong, Xuyan Guo, Xiaoyang Qiao, Shifang Guo, Lei Zhang, Mingxi Wan, Yujin Zong
Journal: Advanced Healthcare Materials (2019)

Abstract Sonodynamic therapy (SDT) not only has greater tissue‐penetrating depth compared to photo‐stimulated therapies, but also can also trigger rapid drug release to achieve synergistic sonochemotherapy. Here, reactive oxygen species (ROS)‐responsive IR780/PTL‐ nanoparticles (NPs) are designed by self‐assembly, which contain ROS‐cleavable thioketal linkers (TL) to promote paclitaxel (PTX) release during SDT. Under ultrasound (US) stimulation, IR780/PTL‐NPs produce high amounts of ROS, which not only induces apoptosis in human glioma (U87) cells but also boosts PTX released by decomposing the ROS‐sensitive TL. In the U87 tumor‐bearing mouse model, the IR780/PTL‐NPs releases the drug at the target sites in a controlled manner upon US irradiation, which significantly inhibits tumor growth and induces apoptosis in the tumor tissues with no obvious toxicity. Taken together, the IR780/PTL‐NPs are a novel platform for sonochemotherapy, and can control the spatio‐temporal release of chemotherapeutic drugs during SDT.
Fine specificity of NKT cells against GD3 ganglioside and identification of GM3 as an inhibitory NKT cell ligand
Authors: Jun-Eui Park, Dianna Wu, Sharon Lu, Paul Chapman
Journal: Cancer Research (2007)

5118  GD3, a ganglioside expressed on melanoma, is the only tumor-associated glycolipid described so far that can induce a CD1d-restricted NKT cell response. We analyzed the fine specificity of GD3-reactive NKT cells and discovered that immunization with GD3 induced two populations of GD3-reactive NKT cells. One population was CD4+CD8- and was specific for GD3; the other population was CD4-CD8- and cross-reacted with GM3 in a CD1d-restricted manner. GD3-reactive NKT cells did not cross-react with GM2, GD2 or lactosylceramide indicating the T-cell receptors that react with GD3 recognize glucose-galactose linked to at least one N-acetyl-neuraminic acid but will not accommodate a terminal N-acetylgalactosamine. Immunization with GM2, GM3, GD2, or lactosylceramide did not induce an IL-4 or IFN-γ NKT cell response against these glycolipids. Co-immunization or GM3-loaded with GD3-loaded APCs suppressed the NKT cell response to GD3 in a CD1d-restricted manner. This suppressive effect was specific for GM3 and was a local effect lasting 2-4 days. In vitro, GM3-loaded APCs also suppressed the IL-4 response of NKT cells to αGalCer. GM3 is the first inhibitory NKT cell ligand to inhibit an in vivo NKT cell response.
Quantitative detection of intraabdominal floating tumor cells and clusters using flowcytometry in patients with peritoneal carcinomatosis.
Authors: Joji Kitayama, Takao Kamei, Shigenobu Emoto, Hironori Yamaguchi, Hironori Ishigami
Journal: Journal of Clinical Oncology (2013)

e15027 Background: Peritoneal metastasis (P) is the most life-threatening types of metastasis in patients with gastrointestinal cancer. Although the presence of tumor cells in peritoneal cavity is evaluated with microscopic observation by pathologists (Cy) or detection of mRNA of tumor specific molecules, no reliable method is available to quantify the accurate volume of tumor cells. Methods: Acsites or peritoneal lavages were recovered from 72 patients who underwent abdominal surgery for gastrointestinal cancer. In patients who received intraperitoneal (IP) chemotherapy for peritoneal metastasis, 40 samples were obtained from subcutaneous intraperitoneal access port during the course of chemotherapy. In those 112 samples, cells were recovered by centrifugation, fixed and immunostained with mAbs to CD45 and to CD326 (EpCAM). Using FACS analysis, CD326(+)CD45(-) and CD45(+)CD326(-) cells were determined as tumor cells (T) and leukocytes (L), respectively, and T/L ratio was calculated. Results: In 72 patients with surgery, Median (M) of T/L ratio of the P(+) patients was 15.3% (0%-751.3%), which was significantly higher than P(-) patients (M=0%, 0%-2.1%, p&lt;0.001). In P1 patients, 50 samples which was determined as positive cytology (Cy+) showed higher T/L ratio as compared with 33 samples with Cy (-) (M=23.0%, 0.3%-751.3% vs M=0.53%, 0%-3.5%, p&lt;0.0001). In 17 patients who underwent IP chemotherapy, T/L ratio was markedly decreased after chemotherapy (M=75%, 0.2%-339.0% vs M=0.16%, 0%-35.0%, p&lt;0.0001) and the response was more sensitive than Cy. Moreover, the MST of the 21 P1 patients who showed T/L ratio less than 10% at initial examination was 459 days, while MST of 8 P1 patients whose CT/L ratio was more than 10% was 188 day (p&lt;0.0012). Conclusions: T/L ratio measured with flowcytometry well reflects the total volume of intraperitoneal tumor cells and could be a reliable biomarker to predict the prognosis as well as effectiveness of IP chemotherapy in P1 patients in gastrointestinal cancer.
Association Between Clinical Practice Group Adherence to Quality Measures and Adverse Outcomes Among Adult Patients With Diabetes
Authors: Lauren G. Gilstrap, Michael E. Chernew, Christina A. Nguyen, Sartaj Alam, Barbara Bai, J. Michael McWilliams, Bruce E. Landon, Mary Beth Landrum
Journal: JAMA Network Open (2019)

Clinical practice group performance on quality measures associated with chronic disease management has become central to reimbursement. Therefore, it is important to determine whether commonly used process and disease control measures for chronic conditions correlate with utilization-based outcomes, as they do in acute disease.To examine the associations among clinical practice group performance on diabetes quality measures, including process measures, disease control measures, and utilization-based outcomes.This retrospective, cross-sectional analysis examined commercial claims data from a national health insurance plan. A cohort of eligible beneficiaries with diabetes aged 18 to 65 years who were enrolled for at least 12 months from January 1, 2010, through December 31, 2014, was defined. Eligible beneficiaries were attributed to a clinical practice group based on the plurality of their primary care or endocrinology office visits. Data were analyzed from October 1, 2018, through April 30, 2019.For each clinical practice group, performance on current diabetes quality measures included 3 process measures (2 testing measures [hemoglobin A1c {HbA1c} and low-density lipoprotein {LDL} testing] and 1 drug use measure [statin use]) and 2 disease control measures (HbA1c <8% and LDL level <100 mg/dL). The rates of utilization-based outcomes, including hospitalization for diabetes and major adverse cardiovascular events (MACEs), were also measured.In this cohort of 652 258 beneficiaries with diabetes from 886 clinical practice groups, 42.9% were aged 51 to 60 years, and 52.6% were men. Beneficiaries lived in areas that were predominantly white (68.1%). At the clinical practice group level, except for high correlation between the 2 testing measures, correlations among different quality measures were weak (r range, 0.010-0.244). Rate of HbA1c of less than 8% had the strongest correlation with hospitalization for MACE (r = -0.046; P = .03) and diabetes (r = -0.109; P < .001). Rates of HbA1c control at the clinical practice group level were not significantly associated with likelihood of hospitalization at the individual level. Performance on the process and disease control measures together explained 3.9% of the variation in the likelihood of hospitalization for a MACE or diabetes at the individual level.In this study, performance on utilization-based measures-intended to reflect the quality of chronic disease management-was only weakly associated with direct measures of chronic disease management, namely, disease control measures. This correlation should be considered when determining the degree of financial emphasis to place on hospitalization rates as a measure of quality in treatment of chronic diseases.