tbuckley/cabot-search huggingface dataset:
Natural history and prognosis of untreated stage I epithelial ovarian carcinoma.
Authors: F Y Ahmed, E Wiltshaw, R P A'Hern, B Nicol, J Shepherd, P Blake, C Fisher, M E Gore
Journal: Journal of Clinical Oncology (1996)

PURPOSE The aim of this study was to investigate the independent significance of prognostic factors in stage I invasive epithelial ovarian cancer (EOC). PATIENTS AND METHODS Between 1980 and 1994, all patients with stage I EOC (borderline tumors excluded) following surgical resection were entered onto this study. No patient received adjuvant therapy and patients were monitored as follows: years 1 to 2-physical examination and serum CA125 every 3 months and computed tomographic (CT) scan every 6 months; years 3 to 5-physical examination and serum CA125 every 6 months and CT scan yearly; years 5 to 10-annual physical examination and serum CA125, with CT scan if clinically indicated. RESULTS A total of 194 patients entered the study. The median patient age was 54 years (range, 15 to 83), and the median follow-up duration 54 months (range, 7 to 157). Five-year survival rates were as follows: stage IA, 93.7%; stage IB, 92%; and stage IC, 84%. Multivariate analysis using Cox's regression identified grade (P &lt; .001), presence of ascites (P = .05), and surface tumor (P &lt; .01) as independent poor prognostic factors. International Federation of Gynecology and Obstetrics (FIGO) substage did not appear to have independent prognostic significance. Intraoperative capsule rupture was not found to be prognostically significant. The impact of pre-operative rupture remains unclear. CONCLUSION This is an important series, as no patient received adjuvant therapy, and represents the natural history of surgically resected stage I EOC.
HLA class II sequence variants influence tuberculosis risk in populations of European ancestry
Authors: Gardar Sveinbjornsson, Daniel F Gudbjartsson, Bjarni V Halldorsson, Karl G Kristinsson, Magnus Gottfredsson, Jeffrey C Barrett, Larus J Gudmundsson, Kai Blondal, Arnaldur Gylfason, Sigurjon Axel Gudjonsson, Hafdis T Helgadottir, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Ari Karason, Ljiljana Bulat Kardum, Jelena Knežević, Helgi Kristjansson, Mar Kristjansson, Arthur Love, Yang Luo, Olafur T Magnusson, Patrick Sulem, Augustine Kong, Gisli Masson, Unnur Thorsteinsdottir, Zlatko Dembic, Sergey Nejentsev, Thorsteinn Blondal, Ingileif Jonsdottir, Kari Stefansson
Journal: Nature Genetics (2016)
Clinical usefulness of the oxygen uptake efficiency in pulmonary embolism
Authors: Jinming Liu, Shujuan Chen, Wenlan Yang, Jian Guo
Journal: European Respiratory Journal (2014)

OBJECTIVES We sought to study the oxygen uptake efficiency, an index of cardiopulmonary functional reserve that can be based upon a submaximal exercise effort, in pulmonary embolism (PE) by performing the cardiopulmonary exercise test (CPET).  METHODS The cardiopulmonary exercise test with simultaneous respiratory gas measurement were performed in fifty PE patients and fifty healthy individuals. All subjects also underwent the pulmonary function test (PFT).  RESULTS (1) In compared with the controls, the PE patients had lower peak oxygen uptake (peakVO 2 ), oxygen uptake efficiency slope (OUES), oxygen uptake efficiency plateau (OUEP) and oxygen uptake efficiency at anaerobic threshold (OUE@AT) (P 2  /VE) at warming up, AT and peak exercise but the rest, indicated statistically lower than the controls. The OUE in normal subjects increased as unloaded exercise began, and then increased further to OUEP just before the AT. Thereafter, the OUE decreased gradually until peak exercise. In contrast, the rate of changes of the OUE in PE patients was relatively mild during exercise. (3) OUES, OUEP, OUE@AT correlated strongly with peakVO 2  and DL CO %pred (r=0.712,0.404,0.414; p  CONCLUSIONS The oxygen uptake efficiency of patients with PE decreases. The OUE is an objective, reproducible measure of cardiopulmonary reserve that does not require a maximal exercise effort. Therefore, OUE could be helpful to assess exercise performance in PE patients that unable to perform a maximal exercise test in early recovery stage.
Enhancement of Production of Superoxide Anion by Human Polymorphonuclear Leukocytes Exposed to Products of the HT-29 Human Colonic Adenocarcinoma Cell Line
Authors: D Bettetini, F Garrouste, M Remacle-Bonnet, J M Culouscou, J Marvaldi, G Pommier
Journal: JNCI Journal of the National Cancer Institute (1986)

Generation of superoxide anion (O2-) by human polymorphonuclear leukocytes (PMNs) in response to stimulation by opsonized zymosan was enhanced about 100% by prior exposure of the PMNs to human colonic adenocarcinoma cells (HT-29 cell line) or their conditioned culture medium. In addition, HT-29 cells produced substances that had an appreciable chemokinetic activity on PMNs. These tumor-secreted substances appeared to act directly on the PMNs rather than indirectly by interacting with nonadherent mononuclear cells, e.g., lymphocytes. Such a priming activity to display enhanced production of O2- was also found in conditioned medium from F344 rat FR3T3 embryonic fibroblasts but not in conditioned medium from HT-29 repolarized cells (by culture in galactose-containing medium) or from nontumorous human colonic mucosa explants. Such active substances may be important in the host-tumor relationship and, therefore, in the outcome of tumor growth.
A randomized, open-label, phase I/II trial of gemcitabine plus nab-paclitaxel with or without FG-3019 as neoadjuvant chemotherapy in locally advanced, unresectable pancreatic cancer.
Authors: Flavio G. Rocha, Scott Helton, Vincent J. Picozzi
Journal: Journal of Clinical Oncology (2015)

TPS500 Background: Only 15% of patients with pancreatic ductal adenocarcinoma (PDAC) are eligible for resection. Patients with locally advanced PDAC may become candidates for surgery following donwstaging with neoadjuvant therapy. PDAC often exhibits a high degree of desmoplasia, characterized by extensive connective tissue stroma. FG-3019 is a recombinant human monoclonal antibody that binds to connective tissue growth factor and significantly reduces tumor growth, neovascularization, and metastases in mouse models of PDAC. Therefore, FG-3019 may change the fibrotic character of PDAC to one more amenable to resection. In a phase I trial of stage III/IV patients, FG-3019 did not add toxicity when combined with gemcitabine and erlotinib. Methods: Phase 1/2, randomized, open-label trial to evaluate safety and tolerability of gemcitabine plus Nab-paclitaxel with FG-3019 or gemcitabine plus Nab-paclitaxel in subjects with locally advanced, unresectable PDAC (clinicaltrials.gov #NCT02210559). Primary endpoint is treatment-related adverse events. Secondary endpoints include R0 resection rate, surgical complications, tumor response, and survival. Patients with biopsy-proven PDAC are included following radiographic and laparoscopic confirmation of irresectability and no metastases. Sample size of 40 is based on clinical judgment for initial exploration of safety, tolerability, and treatment effect. Each cycle is 28 days and subjects receive up to six cycles of treatment. Those who complete treatment undergo resection based on the following criteria: reduction in CA 19-9 level by more than 50%, FDG-PET SUV max decrease by &gt;30%, or radiological tumor response per RECIST to meet the definition of resectable or borderline resectable. Safety will be assessed through adverse event monitoring, clinical laboratory testing, ECG, ECOG performance status, vital signs, and physical exam until 28 days after the last FG-3019 infusion. All resected subjects will be followed for 30 days after discharge and undergo safety assessment per standard of care. Since the trial opened in 8/2014, we have enrolled 1/40 patients. Clinical trial information: NCT02210559.
Several factors must have a role in improved figures
Authors: A. Carnon, D. Hole, C. Gillis, D. Brewster
Journal: BMJ (1996)

EDITOR,—Mike Quinn and Elizabeth Allen's suggestion that better treatment in breast cancer has led to a fall in mortality from 1990 onwards is interesting.1 As the authors imply, the widespread use of tamoxifen can be only part of the explanation.

A more direct way of looking at the outcome of changes in treatment …
Should we dream the impossible dream? The meaning of long-term survival in metastatic breast cancer.
Authors: G W Sledge
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.8.2191 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8708706 Should we dream the impossible dream? The meaning of long-term survival in metastatic breast cancer. G W Sledge JrxG W Sledge JrSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.8.2191 First Page PDF © 1996 by American Society of Clinical Oncology
Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone.
Authors: F Roila, M Tonato, F Cognetti, E Cortesi, G Favalli, M Marangolo, D Amadori, M A Bella, V Gramazio, D Donati
Journal: Journal of Clinical Oncology (1991)

Ondansetron (OND) is a new 5-HT3 receptor antagonist that give complete protection from emesis/nausea in approximately 50% of cisplatin (CDDP)-treated patients. To evaluate if dexamethasone (DEX) added to OND increases antiemetic efficacy, we carried out a double-blind randomized crossover study to compare the antiemetic activity of OND with OND plus DEX. One hundred two chemotherapy-naive patients (44 women and 58 men) scheduled to receive CDDP chemotherapy at doses greater than or equal to 50 mg/m2 entered the study. Eighty-nine patients completed both cycles with the following results: complete protection from emesis/nausea was obtained in 57/59 patients (64.0%/66.3%) with OND and in 81/79 (91.0%/88.8%) with OND plus DEX (P = .0005/P = .0021). At the end of the study, 53% of the patients expressed a treatment preference, and of these, 74% chose OND plus DEX compared with 26% who preferred OND alone, a statistically significant difference (P less than .003). Side effects were very mild and not significantly different between the two treatments. We conclude that OND plus DEX is more efficacious than OND in protecting patients from CDDP-induced emesis and nausea.
Hepatitis C Virus Treatment and Persons Who Inject Drugs
Authors: Elinore F. McCance-Katz, Ronald O. Valdiserri
Journal: Annals of Internal Medicine (2016)

Letters2 February 2016Hepatitis C Virus Treatment and Persons Who Inject DrugsElinore F. McCance-Katz, MD, PhD and Ronald O. Valdiserri, MD, MPHElinore F. McCance-Katz, MD, PhDFrom Eleanor Slater Hospital, Cranston, Rhode Island, and Office of HIV/AIDS and Infectious Disease Policy, U.S. Department of Health and Human Services, Washington, DC.Search for more papers by this author and Ronald O. Valdiserri, MD, MPHFrom Eleanor Slater Hospital, Cranston, Rhode Island, and Office of HIV/AIDS and Infectious Disease Policy, U.S. Department of Health and Human Services, Washington, DC.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L15-0486 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We appreciate Dr. Grebely and colleagues' comments because they provide the opportunity for several clarifications related to our opinion advocating for HCV treatment for drug users. We wrote our article to underscore the point that persons with a history of injection and other drug use can be successfully treated for HCV infection. Although active injection drug use may not pose an absolute contraindication to HCV therapy, we believe that successful treatment of a substance use disorder helps to ensure optimal outcomes for the treatment of other relevant comorbidities, including HCV infection. We also maintain that engagement of injection ...Reference1. Treloar C, Rance J, Backmund M. Understanding barriers to hepatitis C virus care and stigmatization from a social perspective. Clin Infect Dis. 2013;57 Suppl 2:S51-5. [PMID: 23884066] doi:10.1093/cid/cit263 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Eleanor Slater Hospital, Cranston, Rhode Island, and Office of HIV/AIDS and Infectious Disease Policy, U.S. Department of Health and Human Services, Washington, DC.Disclosures: Authors disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0007. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoHepatitis C Virus Treatment and Injection Drug Users: It Is Time to Separate Fact From Fiction Elinore F. McCance-Katz and Ronald O. Valdiserri Hepatitis C Virus Treatment and Persons Who Inject Drugs Jason Grebely , Gregory J. Dore , Robert Greenwald , Tracy Swan , Soumitri Barua , and Lynn E. Taylor Metrics 2 February 2016Volume 164, Issue 3Page: 203-204KeywordsAddictsConflicts of interestDisclosureDrug addictionDrug therapyDrugsHealth care providersHepatitis C virusInjecting drug usersOpioid use disorder ePublished: 2 February 2016 Issue Published: 2 February 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer's disease
Authors: Jonathan Cedernaes, Ricardo S. Osorio, Andrew W. Varga, Korey Kam, Helgi B. Schiöth, Christian Benedict
Journal: Sleep Medicine Reviews (2016)

During wakefulness, extracellular levels of metabolites in the brain increase. These include amyloid beta (Aβ), which contributes to the pathogenesis of Alzheimer's disease (AD). Counterbalancing their accumulation in the brain, sleep facilitates the removal of these metabolites from the extracellular space by convective flow of the interstitial fluid from the para-arterial to the para-venous space. However, when the sleep-wake cycle is disrupted (characterized by increased brain levels of the wake-promoting neuropeptide orexin and increased neural activity), the central nervous system (CNS) clearance of extracellular metabolites is diminished. Disruptions to the sleep-wake cycle have furthermore been linked to increased neuronal oxidative stress and impaired blood–brain barrier function – conditions that have also been proposed to play a role in the development and progression of AD. Notably, recent human and transgenic animal studies have demonstrated that AD-related pathophysiological processes that occur long before the clinical onset of AD, such as Aβ deposition in the brain, disrupt sleep and circadian rhythms. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted sleep-wake cycles, which is able to accelerate the development and progression of this disease.
Recombinant N–Terminal Slit2 Inhibits TGF-β–Induced Fibroblast Activation and Renal Fibrosis
Authors: Darren A. Yuen, Yi-Wei Huang, Guang-Ying Liu, Sajedabanu Patel, Fei Fang, Joyce Zhou, Kerri Thai, Ahmad Sidiqi, Stephen G. Szeto, Lauren Chan, Mingliang Lu, Xiaolin He, Rohan John, Richard E. Gilbert, James W. Scholey, Lisa A. Robinson
Journal: Journal of the American Society of Nephrology (2016)

Fibrosis and inflammation are closely intertwined injury pathways present in nearly all forms of CKD for which few safe and effective therapies exist. Slit glycoproteins signaling through Roundabout (Robo) receptors have been described to have anti-inflammatory effects through regulation of leukocyte cytoskeletal organization. Notably, cytoskeletal reorganization is also required for fibroblast responses to TGF- β . Here, we examined whether Slit2 also controls TGF- β –induced renal fibrosis. In cultured renal fibroblasts, which we found to express Slit2 and Robo-1, the bioactive N–terminal fragment of Slit2 inhibited TGF- β –induced collagen synthesis, actin cytoskeletal reorganization, and Smad2/3 transcriptional activity, but the inactive C–terminal fragment of Slit2 did not. In mouse models of postischemic renal fibrosis and obstructive uropathy, treatment with N-terminal Slit2 before or after injury inhibited the development of renal fibrosis and preserved renal function, whereas the C-terminal Slit2 had no effect. Our data suggest that administration of recombinant Slit2 may be a new treatment strategy to arrest chronic injury progression after ischemic and obstructive renal insults by not only attenuating inflammation but also, directly inhibiting renal fibrosis.
A novel Aurora B kinase inhibitor with potent anticancer activity either as a single agent or in combination with chemotherapy
Authors: J. S. Nair, A. Tse, N. Keen, G. K. Schwartz
Journal: Journal of Clinical Oncology (2004)

9568 Background: Aurora kinases are serine/threonine kinases that play a key role in regulating mitosis. Elevated expression of two of the human homologues, Aurora A and B, has been reported in a wide variety of tumors and frequently correlates with a poor prognosis. Aurora B has been reported to play an important role at the spindle checkpoint. Compound 677 is a novel, selective inhibitor of Aurora B that targets cell division in proliferating tumor cells. We elected to test Compound 677 as a novel cancer therapy. Methods: Hct116 colon cancers with intact p53 (p53+/+), absent p53 (p53−/−) and absent p21 (p21−/−), were treated with increasing concentrations of Compound 677 as a single agent and in combination with chemotherapy. Results: Colony formation analyses revealed an IC50 of 4 nM for p53+/+ cells while p53−/− and p21−/− cells displayed increased sensitivity to Compound 677 (IC50 2.0 and 1.5 nM, respectively). Flow cytometric analysis of each cell line, indicated polyploidy with 16 N and 32 N cells with 677 concentrations as low as 5 nM, as early as 15 hours after drug exposure, accompanied by inhibition of phosphohistone H3 (an Aurora B substrate). Compound 677 induced multinucleation of p53+/+ cells at the first cell cycle, followed by failure of cell division. Normal bipolar spindles were formed, but chromatin segregation was inhibited. Apoptosis was not significant up to 6 days post treatment. Colony formation assays using Compound 677 in combination with SN-38 (the active metabolite of CPT-11), docetaxel, vinorelbine, gemcitabine, oxaliplatin or 5-fluorouracil revealed a more than additive effect with all combinations. However, SN-38 and gemcitabine administered prior to Compound 677 inhibited multinucleation, antagonizing the effects of combination therapy. Conclusions: Compound 677 is a potent inhibitor of cell growth in proliferating cancer cells, both as a single agent and in combination with chemotherapy. Initial studies suggest that administration sequence may influence the outcome when an Aurora B kinase inhibitor is co-administered with chemotherapy. Further work is ongoing to optimise scheduling. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca
Timing of expression of the core clock gene <i>Bmal1</i> influences its effects on aging and survival
Authors: Guangrui Yang, Lihong Chen, Gregory R. Grant, Georgios Paschos, Wen-Liang Song, Erik S. Musiek, Vivian Lee, Sarah C. McLoughlin, Tilo Grosser, George Cotsarelis, Garret A. FitzGerald
Journal: Science Translational Medicine (2016)

The absence of Bmal1, a core clock gene, results in a loss of circadian rhythms, an acceleration of aging, and a shortened life span in mice. To address the importance of circadian rhythms in the aging process, we generated conditional Bmal1 knockout mice that lacked the BMAL1 protein during adult life and found that wild-type circadian variations in wheel-running activity, heart rate, and blood pressure were abolished. Ocular abnormalities and brain astrogliosis were conserved irrespective of the timing of Bmal1 deletion. However, life span, fertility, body weight, blood glucose levels, and age-dependent arthropathy, which are altered in standard Bmal1 knockout mice, remained unaltered, whereas atherosclerosis and hair growth improved, in the conditional adult-life Bmal1 knockout mice, despite abolition of clock function. Hepatic RNA-Seq revealed that expression of oscillatory genes was dampened in the adult-life Bmal1 knockout mice, whereas overall gene expression was largely unchanged. Thus, many phenotypes in conventional Bmal1 knockout mice, hitherto attributed to disruption of circadian rhythms, reflect the loss of properties of BMAL1 that are independent of its role in the clock. These findings prompt reevaluation of the systemic consequences of disruption of the molecular clock.
Apoptotic and immunomodulatory effects of green tea extracts (GTE) on chemoresistant human tumor cells
Authors: D. P. Braun, D. M. Johnson, N. G. Katsantonis, K. Bhesaniya, E. D. Staren
Journal: Journal of Clinical Oncology (2009)

e22101 Background: GTE and Epigallocatechin 3-gallate (EGCG), the most abundant polyphenol in GTE, have been shown to exert inhibitory effects on carcinogenesis; modulatory effects on tumor proliferation and differentiation; and immunomodulatory effects on tumor immunity in different pre-clinical models. These pluripotent effects suggest that GTE may have clinical activity that could be exploited for treatment of chemo-insensitive but immunologically responsive tumors. Thus, the present study investigated the effects of EGCG on the proliferation and immunologic sensitivity of human renal cell cancer (RCC) and malignant melanoma (MM) cell lines. Methods: Human RCC (769-P) and MM (A375) cell lines were tested following incubation in media ± 21.8μM EGCG, a pharmacologically-achievable concentration produced by 8, 200mg capsules GTE daily. Tumor proliferation was assessed by MTS assay; lytic sensitivity to IL2-activated human peripheral blood lymphocytes (IL2PBL) by 51 Chromium release assay; and gene expression by quantitative RT-PCR assay. Results: EGCG produced significant inhibition of proliferation of both RCC and MM cells (61.5% and 67.3% of media control values respectively; p&lt;0.01 by 2-tailed, paired t test). EGCG also caused significantly increased expression (≥ 2 times (×) media control values) of pro-apoptotic genes in both RCC: BCL2L1 (5.4×); BCL2L10 (7.9×); BIK (2.9×); Caspase 5 (6.3×); and Caspase 14 (6.3×) and MM cells: Caspase8 (2X) and Card6 (2.5X). Unfortunately, EGCG pre-treatment also decreased the sensitivity of RCC (43% of control) and MM (53% of control) to IL2PBL-mediated lysis (p&lt;0.01 respectively). This occured in association with significant upregulation of Fas ligand mRNA in RCC (6.3×) and TRAF2 mRNA in MM (33 ×). Conclusions: The results of this pre-clinical study demonstrate that EGCG exerts significant antiproliferative effects against human RCC and MM cells in vitro in association with increased expression of different pro-apoptotic genes. Unfortunately, EGCG-treated cells also demonstrated reduced sensitivity to lysis by IL2-activated human lymphocytes. Taken together, the results suggest that GTE may have activity in vivo in patients against chemoresistant RCC or MM but should not be used in conjunction with IL2 therapy. No significant financial relationships to disclose.