tbuckley/cabot-search huggingface dataset:
Ectopic Hematopoiesis in Peritoneal Tumor Nodules Induced by the Myeloproliferative Sarcoma Virus in DBA/2 Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: F Smadja-Joffe, M C Le Bousse-Kerdiles, A M Bertoli, V Degiorgis, B Caillou, C Jasmin
Journal: JNCI Journal of the National Cancer Institute (1986)

Tumor nodules composed of fibroblasts, large undifferentiated cells, granulocytes, and small lymphocytes develop in the spleens of adult DBA/2 mice infected with the myeloproliferative sarcoma virus (MPSV). They spread thereafter in the organism, and at the terminal stage of the disease they are especially numerous on the peritoneal membrane. The present study, performed on those tumor nodules to avoid contamination by exogenous hematopoietic cells, demonstrated that they were sites of granulopoiesis, which may have occurred via the local differentiation of granulomacrophage precursor cells (GM-CFC) and perhaps also from pluripotent hematopoietic stem cells, since these two populations were present in the tumor nodules (25 +/- 11 and 13 +/- 10, respectively, per 5-10(5) cells). Almost all (88%) those GM-CFC were able to clone in vitro without added colony-stimulating factor. A comparative study with the Moloney murine sarcoma virus-induced tumor indicated that the local production of hematopoiesis-stimulating factors was not sufficient to allow such ectopic granulopoiesis. These results imply the presence of a specific hematopoietic microenvironment in the MPSV-induced tumor nodules.
MARKED UREMIA WITH RECOVERY; REPORT OF A CASE
Authors: R. O.  BOWMAN, S.  WOLPAW
Journal: Annals of Internal Medicine (1937)

Case Reports1 July 1937MARKED UREMIA WITH RECOVERY; REPORT OF A CASER. O. BOWMAN, Ph.D., S. WOLPAW, M.D.R. O. BOWMAN, Ph.D.Search for more papers by this author, S. WOLPAW, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-11-1-209 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCASE REPORTJ. F., a 29-year-old white woman, was admitted to the Surgical Service of the Cleveland City Hospital on September 12, 1933.According to the patient's history her last menstrual period had occurred on July 8, 1933. Having missed her August period and believing herself to be pregnant she had attempted to produce an abortion by the use of various oral medications, the exact nature of which we were unable to determine. Failing in this attempt an abortion was induced on September 7, by packing the vagina with gauze. The pack was removed after one day and was followed...Bibliography1. SELMANLENIGAR JJCR: A case of marked creatinemia with recovery, Jr. Lab. and Clin. Med., 1933, xviii, 1032-1034. Google Scholar2. MONTZKA K: Über tödliche Quecksilbervergiftung von der Scheide aus, Med. Klin., 1933, xxix, 1343-1346. Google Scholar3. MINTZ ER: Some remarks on the treatment of bichloride poisoning with a presentation of 21 cases, New Eng. Jr. Med., 1933, ccviii, 1189-1194. CrossrefGoogle Scholar4. Female-Weakness "Cures." Pamphlet of American Medical Association. Google Scholar5. BRENOT MR: Abstract of case report of fatal poisoning by apiol, Ther. Monatschr., 1916, xxx, 56. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Providence, Rhode Island*Received for publication November 18, 1936.From Cleveland City Hospital, Cleveland, Ohio. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySymptomatologie, Pathogenese und Therapie der akuten und chronischen Pseudourämie und der echten Urämie 1 July 1937Volume 11, Issue 1Page: 209-212KeywordsPregnancyVagina ePublished: 1 December 2008 Issue Published: 1 July 1937 PDF downloadLoading ...
NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions
Authors: Katerina Vlantis, Andy Wullaert, Apostolos Polykratis, Vangelis Kondylis, Marius Dannappel, Robin Schwarzer, Patrick Welz, Teresa Corona, Henning Walczak, Falk Weih, Ulf Klein, Michelle Kelliher, Manolis Pasparakis
Journal: Immunity (2016)

Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired epithelial responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD). IEC-specific ablation of nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis and impaired antimicrobial factor expression in the ileum, as well as colonocyte apoptosis and microbiota-driven chronic inflammation in the colon. Combined RelA, c-Rel, and RelB deficiency in IECs caused Paneth cell apoptosis but not colitis, suggesting that NEMO prevents colon inflammation by NF-κB-independent functions. Inhibition of receptor-interacting protein kinase 1 (RIPK1) kinase activity or combined deficiency of Fas-associated via death domain protein (FADD) and RIPK3 prevented epithelial cell death, Paneth cell loss, and colitis development in mice with epithelial NEMO deficiency. Therefore, NEMO prevents intestinal inflammation by inhibiting RIPK1 kinase activity-mediated IEC death, suggesting that RIPK1 inhibitors could be effective in the treatment of colitis in patients with NEMO mutations and possibly in IBD.
Does time interval between surgery and adjuvant chemotherapy initiation modify treatment efficacy in operable, breast cancer patients? French Adjuvant Study Group (FASG) results
Authors: P. Kerbrat, H. Roche, P. Fumoleau, J. Bonneterre, P. Romestaing, P. Fargeot, M. Namer, A. Monnier, P. Montcuquet, M.-J. Goudier, E. Luporsi
Journal: Journal of Clinical Oncology (2005)

660 We analyzed retrospectively the influence of delay between surgery and adjuvant chemotherapy on disease-free survival (DFS) in operable, breast cancer patients. Methods - Among eight FASG trials, 2,602 patients were assessable: 1,667 received chemotherapy; 935 chemoendocrine therapy. Chemotherapy: epirubicin-based regimens (50, 75, or 100 mg/m2, 3 or 6 cycles). Hormonotherapy: tamoxifen 30 mg/day 3 years started at the first chemotherapy cycle. Radiotherapy was delivered after the 3rd cycle in 30% of patients, and after the 6th cycle in the others. We separated time interval between surgery and chemotherapy in 3 groups: < 28 days (I), 28 to 42 days (II), and > 42 days (III). Median follow-up: 9 years. Results - The distribution of patients was 1,614 (I), 883 (II) and 105 (III). The 9-year DFS rates were 60%, 58%, and 49%, respectively (P = .01). Pairwise comparisons demonstrated a significant difference between groups I and II (P = .04), whereas no difference was found between groups II and III (P = .12). The comparison between groups I and II showed. The multivariate analysis showed that, in patients receiving chemotherapy, there was a trend for a higher risk of relapse if chemotherapy was delivered > 28 days after surgery (HR = 0.85; CI 95%, 0.65–1.05; P = .06). There was no influence of the delay in chemotherapy initiation for patients receiving chemoendocrine therapy. Conclusion - A delay > 28 days to start chemotherapy in patients with the worse prognostic factors seems to be deleterious. This effect was not found in patients receiving chemoendocrine therapy if chemotherapy was delivered within 42 days. We can’t clearly conclude if the delay exceeded 42 days as few patients were in this situation. No significant financial relationships to disclose.
Is There a Future for AKT Inhibitors in the Treatment of Cancer?
Authors: Valerie M. Jansen, Ingrid A. Mayer, Carlos L. Arteaga
Journal: Clinical Cancer Research (2016)

Abstract An AKT inhibitor plus an antiestrogen exhibited no significant clinical activity in patients with ER+/HER2− breast cancer despite laboratory studies supporting an antitumor effect for both drugs combined. These results raise concerns about the development of AKT inhibitors in unselected patients whose tumors have unknown dependence on the PI3K/AKT pathway. Clin Cancer Res; 22(11); 2599–601. ©2016 AACR. See related article by Ma et al., p. 2650
Abstract 189: Changes in Initial Quantitative VF Score as a Function of EMS Response Time
Authors: Alan B Williams, Robert A Silverman, Dawn Jorgenson, Doug A Isaacs, John P Freese
Journal: Circulation (2014)

Introduction:  EMS response intervals have been correlated with increased return of spontaneous circulation (ROSC), as well as improved survival to hospital admission and discharge. Response intervals have also been associated with increased likelihood of ventricular fibrillation (VF) as the presenting rhythm, as well as crude VF waveform amplitude. The role of bystander CPR (B-CPR) has been extensively studied, with some studies suggesting a more limited contribution to survival. We sought to analyze correlations between EMS response time, B-CPR and VF waveform properties.   Methods:  We performed a retrospective analysis of data derived from an international randomized controlled trial utilizing a VF waveform algorithm in patients with out of hospital cardiac arrest (OOHCA). Standard Utstein definitions were used. EMS response times were calculated from the time calls were received until EMS personnel arrived at the incident location. Quantitative VF scores were calculated using a proprietary algorithm.   Results:  There were a total of 752 bystander-witnessed VF arrests for which B-CPR and EMS response times were known. Those patients who received B-CPR (n=290) had a mean normalized VF score of 0.13 (sd=0.07), while those not receiving B-CPR (n=462) had a mean initial VF score of 0.11 (sd=0.07), (p   Conclusions:  Bystander CPR improves the likelihood that OOHCA patients will present with VF characteristics amenable to immediate shock. EMS response time was not associated with increased quantitative VF score when B-CPR occurred. These findings suggest a physiologic explanation through which B-CPR may contribute to improved outcomes that has not been previously described. Further research regarding this relationship may aid strategies for optimizing B-CPR and its contribution to OOHCA survival.
Local excision for rectal cancer
Authors: N. N. Baxter, A. K. Stewart, H. Nelson
Journal: Journal of Clinical Oncology (2004)

3615 Background: The treatment of low lying early stage rectal cancer is controversial. Local excision (LE) has been promoted to increase the rate of sphincter preservation, however there are concerns regarding the oncologic adequacy of this procedure as compared to standard radical resection (RR). This study was designed to evaluate nationwide patterns of surgical treatment and survival of early stage rectal cancer using data from the National Cancer Data Base (NCDB). Methods: We examined rectal cancer cases reported to the NCDB during 3 time periods; 1989–91, 1994–6 and 1999–2001. Patients had T1 or T2 rectal cancers that were clinically and pathologically node negative and no neoadjuvant treatment was received. Patterns of treatment over time were examined using the Mantel-Haenszel chi-square test. Associations between treatment and 5-year survival were assessed for individuals treated from 1994–6, using proportionate hazards models to control for demographic covariates. Results: A total of 25,815 patients meeting selection criteria were identified; 28% in the first time period, 36% in the second, and 36% in the third. T1 lesions were identified in 30%. Rates of LE increased over time, both for T1 lesions (22% - 46%, p<0.0001) and T2 lesions (6% - 17%, p<0.0001). LE was more common in T1 lesions, the elderly (>75 yrs), African Americans, and women. Many patients undergoing LE had poorly differentiated tumors. The 5-year survival of patients with T1 lesions was similar in those treated with LE and RR; 77% versus 80%, however survival was worse with LE for those with T2 lesions; 66% versus 73% (p<0.0001). In multivariate modeling for T1 lesions, type of surgical treatment did not have a significant effect on survival. For T2 lesions, LE was associated with worse survival; hazards ratio = 0.82 (95% CI 0.68–0.99). Conclusions: The use of LE for Stage I rectal cancer is increasing, both for T1 lesions and T2 lesions. This does not appear to have negative consequence for T1 lesions, however LE for T2 lesions is associated with worse 5 year survival. Although some of this effect may be due to inadequate staging with local excision, at the current time LE for T2 lesions should be used with great caution. No significant financial relationships to disclose.
Extending platinum-free interval (PFI) in partially platinum-sensitive (PPS) patients (pts) with recurrent ovarian cancer (ROC) treated with trabectedin (Tr) plus pegylated liposomal doxorubicin (Tr+PLD) versus PLD alone: Results from a PPS cohort of a phase III study.
Authors: A. Poveda, S. Tjulandin, B. Kong, M. Roy, S. Chan, E. Filipczyk-Cisarz, H. Hagberg, C. Lebedinsky, T. V. Parekh, B. J. Monk
Journal: Journal of Clinical Oncology (2010)

5012 Background: OVA-301, a phase III study comparing Tr+PLD vs. PLD alone in 672 ROC pts progressing after one prior platinum-based regimen, showed significantly longer progression-free survival (PFS), higher response rate (RR) for the combination by 3 separate assessments: independent radiology (IR), independent oncology (IO) and investigators (IA) and a positive trend for longer survival (OS) (Monk, Ann Oncol 2008 vol 19 Sup8). Methods: PFI > 6 mo was found in 430 (64%) of 672 randomized pts, including 214 (32%) pts with PPS disease (PFI 6-12 mo). Outcomes of this nonplatinum combination on PFS, RR and OS (protocol-specified interim analysis, cutoff May 08) are shown for the PPS population. We evaluated time from randomization to subsequent platinum (SP) and survival time from SP. Results: Baseline characteristics of pts with PPS were balanced and consistent with those of the overall study population. Median (med) no. cycles, 6 (Tr+PLD) vs. 5 (PLD); 40% vs. 24% pts received ≥ 7 cycles. RR and PFS by IR significantly favored Tr+PLD: 33% vs. 15% (p = 0.0041); med PFS 7.4 vs. 5.5 mo (HR 0.65; p = 0.0152), with consistently superior outcomes by both IO and IA. Med OS from randomization was in favor of Tr+PLD: 20.7 vs. 17.2 mo (HR: 0.59; p=0.0090). Proportion of pts receiving SP was comparable in both arms. A significant delay in the administration of SP with the combination (med 15.3 vs. 11.6 mo; HR 0.60, p = 0.0093) was observed. Med survival time from start of SP until death or last contact was 11.0 vs. 9.2 mo (HR 0.72, p = 0.2480). The Tr+PLD safety profile of PPS cohort agreed with that of the overall study population and was consistent with known toxicities of each agent. No new or unexpected toxicities were seen. Conclusions: In the PPS cohort of OVA-301, Tr+PLD induced significantly superior RR, PFS and OS (3.5 mo prolongation in med OS). Significant delay in time to SP and longer survival after SP therapy was seen after this nonplatinum regimen. Safety was manageable rendering a highly favorable benefit/risk ratio in this population with high unmet need for new therapeutic options. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson, PharmaMar PharmaMar Johnson & Johnson, Zeltia Johnson & Johnson Johnson & Johnson
Abstract 19506: The Pulmonary Hypertension Connection Equation Predicts Survival Accurately in a Prospective Population PAH Cohort
Authors: Thenappan Thenappan, Susie McDevitt, Gary Moore, Susan Walker, Mardi Gomberg-Maitland
Journal: Circulation (2010)

Introduction: Contemporary survival in pulmonary arterial hypertension (PAH) is better when compared to the NIH registry, and the NIH equation no longer accurately predicts survival in idiopathic, familial, and anorexigen-associated PAH. We recently developed a new equation, the pulmonary hypertension connection (PHC) equation, based on baseline hemodynamics for predicting survival in patients with idiopathic, familial, and anorexigen-associated PAH. Aim: To validate PHC equation in a combined dataset from PAH drug therapy trials Methods: We performed an ad hoc analysis in idiopathic and heritable PAH patients (n=449) who were prospectively followed for up to 3.5 years in four double-blind, randomized trial, and their open label extension. We compared the rates of actual survival with predicted survival calculated using the PHC equation [(P(t) = e(-A(x,y,z)t), A(x,y,z) = e((−1.270–0.0148x+0.0402y−0.361z)), where P(t) is probability of survival, t the time interval in years, x the mean pulmonary artery pre...
Overexpression of the p73 gene is a novel finding in high-risk B-cell chronic lymphocytic leukemia
Authors: U. Novak, T.J. Grob, G. Baskaynak, U.R. Peters, S. Aebi, D. Zwahlen, M.P. Tschan, K.-A. Kreuzer, E. Oppliger Leibundgut, J.-F. Cajot, A. Tobler, M.F. Fey
Journal: Annals of Oncology (2001)
Distribution of Hepatitis B Surface and Core Antigens in Human Liver Cell Carcinoma and Surrounding Nontumorous Liver&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: S Hirohashi, Y Shimosato, Y Ino, K Kishi
Journal: JNCI Journal of the National Cancer Institute (1982)

The distribution of hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) in surgically removed liver cell carcinomas of 60 Japanese patients was studied by an immunohistochemical method. HBsAg was localized in the cytoplasm, and HBcAg was mainly in the nuclei of normal-appearing liver cells, dysplastic liver cells, and tumor cells. In some instances both HBsAg and HBcAg were contained in the tumor cells and liver cells. HBsAg was found in the nontumorous liver tissue of 30 patients (50%); nine of the HBsAg-containing nontumorous livers also contained HBcAg. HBsAg and/or HBcAg was detected in tumor cells in 7 (23%) of 30 cases with HBsAg-positive liver diseases.
Cytokeratin 19, a Novel Prognostic Biomarker for Hepatocellular Carcinoma, is Regulated By Dna Methylation
Authors: N. Yokomichi, T. Nagasaka, F. Taniguchi, N. Nishida, K. Yoshida, F. Tomokazu, T. Kawai, Y. Takehara, K. Kimura, Y. Mori, R. Inada, Y. Umeda, T. Yagi, A. Goel, T. Fujiwara
Journal: Annals of Oncology (2014)
OC-006 Oncological outcome following ‘watch and wait’ for clinical complete response after pre-operative chemo-radiotherapy in patients with rectal cancer
Authors: A Renehan, L Malcomson, R Emsley, S Gollins, N Scott, ST O’Dwyer
Journal: Gut (2015)

<h3>Introduction</h3> In patients with rectal cancer, management by ‘watch and wait’ (W&amp;W), with potential avoidance of surgical resection (SR), has emerged as a management option following a clinical complete response (cCR) after pre-operative chemoradiotherapy (CRT). However, precise quantification of oncological outcomes after this treatment pathway is unclear. <h3>Method</h3> Between 2010 and 2013, we followed a consecutive series of 259 patients with non-metastatic rectal cancer who completed pre-operative CRT (majority: 45 Gy in 25 daily fractions with concurrent fluoropyrimidine-based chemotherapy). Post-CRT, 31 patients (12%) were considered at a multi-disciplinary meeting to have cCR and offered W&amp;W on a protocolised pathway. We supplemented these cases with a registry of 89 patients managed across four cancer treatment centres in the North West of England and North Wales (total cCRs: 120). Primary endpoint was actuarial rate of intraluminal re-growth. Secondary endpoints were non-intraluminal disease-free survival (niDFS) and colostomy-free survival (CFS). Comparisons with standard care (SR) were performed using propensity score matched-treatment analysis and using time-dependent survival analyses to account for differences in times to W&amp;W decision and salvage SR. <h3>Results</h3> With a mean follow-up from W&amp;W decision of 23 months, there were 36 (30%) intraluminal re-growths (3-year actuarial rate: 35%). Of the 32 intraluminal re-growths without concomitant distant metastases, 25 (78%) underwent subsequent salvage surgery (R0: 24, R1: 1); and 3 underwent Papillon local radiotherapy. After propensity score matching, there were no deleterious effect on niDFS for patients treated by W&amp;W versus SR (hazard ratio, 95% confidence intervals: 0.562; 0.269 to 1.174). However, there was a significant improvement in 3-year CFS rates for patients treated by W&amp;W versus SR: 83% and 54% (log rank, p &lt; 0.001). <h3>Conclusion</h3> Approximately two-thirds of patients with rectal cancer managed by W&amp;W after cCR avoided surgical resection with improvement in colostomy-free survival, without loss of oncological safety. The outcomes from this multi-centred clinical cohort will assist the rectal cancer patient and oncologist with decision making at the outset of long-course CRT. This study was generously supported by the BDRF. <h3>Disclosure of interest</h3> None Declared.
Next-generation sequencing (NGS) of serum microRNA in hepatocellular carcinoma (HCC) patients treated with sorafenib and an mTOR inhibitor.
Authors: Robin Kate Kelley, Aaron N. Chang, Esperanza Anguiano, Jimmy Hwang, Hubert J. Stoppler, Ryan M. McWhirter, Anna L. Parks, Bilal Hameed, Oren K. Fix, Elizabeth M. Wayne, Halla Sayed Nimeiri, Pamela N. Munster, Alan Paul Venook, Andrei Goga
Journal: Journal of Clinical Oncology (2014)

LBA204 Background: Noninvasive biomarkers are urgently needed in HCC. MicroRNA (miRNA) are small, noncoding RNA that regulate mRNA expression and are detectable in tumor tissue and extracellular compartments. miRNA signatures in blood specimens show association with HCC diagnosis but have not been explored as pharmacodynamic or predictive biomarkers. We present a pilot study to identify differentially expressed miRNA using NGS on serum from HCC patients at baseline and on targeted therapy, compared to controls. Methods: Serum samples were obtained from HCC patients enrolled on a clinical trial of sorafenib plus temsirolimus. Control sera were obtained from patients with non-malignant liver diseases (NMLD) and healthy volunteers (HV). Total RNA was extracted using RNAzol followed by library construction for each sample. Small RNA were separated by gel purification and sequenced by Illumina HiSeq 2500 at 5M+ reads per sample. Raw sequencing reads were mapped using Novoalign and quantified. Counts were normalized using an exogenous spike-in miRNA. Comparisons between HCC vs. control and baseline vs. on treatment cohorts were performed by linear regression (one-way ANOVA) and multiple-test corrected using Benjamini-Hochberg statistics. Candidate signature miRNA were derived using fold change, p-value, and abundance cutoffs. Results: Cohorts: HCC baseline (n=23) and paired on treatment (n=20), NMLD (n=12), and HV (n=10). HCC cohort: HBV+/dual 40%, HCV+ 32%. NMLD cohort: HCV+ 83%. Median RNA yield/200 µL was 410 ng (range: 69-1066) for HCC, 406 ng (range: 224-1100) for NMLD. The mapping rate ranged from 10-70%. Elevated AFP was associated with up-regulated miRNA identified in TCGA HCC cases, including miR-10a/b. No significant differences were observed for HBV+ vs. HCV+. Multiple oncomiRs appeared downregulated on treatment including Let-7 and miR-17/92 family members. Some miRNA isoforms were differentially regulated in each cohort. Conclusions: Serum miRNA in HCC patients demonstrate changes on treatment and can be characterized by NGS. Certain miRNA implicated in HCC appeared related to clinical covariates and warrant further study as novel biomarkers.