tbuckley/cabot-search huggingface dataset:
Perioperative anemia as prognostic factor in patients undergoing resection for non-small cell lung cancer
Authors: R. Berardi, T. Tamburrano, A. Fianchini, L. Verdecchia, A. Onofri, A. Santinelli, M. Scartozzi, R. Cellerino, S. Cascinu
Journal: Journal of Clinical Oncology (2004)

7179 Background: In order to explore the clinical implications of anemia as indicator of prognosis, we undertook a study to assess the correlation of preoperative anemia and perioperative blood transfusions with survival in patients with resected non-small cell lung cancer (NSCLC). Methods: From January 1996 through December 2001, 439 patients underwent radical surgery for NSCLC at the Department of Thoracic Surgery of Università Politecnica delle Marche. Results: Median age at surgery was 68 years (range 37 to 84); male/female ratio was 374/65.Two hundreds thirteen patients (48.5%) were diagnosed with adenocarcinoma, 172 patients (39.2%) with squamous cell carcinoma and 25 patients (5.7%) had undifferentiated carcinoma. Pathologic stage of disease was as follows: IA in 77 patients (17.5%), IB in 149 patients (33.9%), IIA in 15 patients (3.4%), IIB 92 patients (21%) and IIIA and IIIB in 89 (20.3%) and 17 (3.9%) of patients respectively. When considering overall patient survival, there was a significant difference in subgroups of patients with lower levels of Hb. In particular survival was worse in patients with Hb ≤10 g/dl versus Hb >10 g/dl (p=0.01). When stratifying patients in three groups on the basis of their Hb level (group 1:Hb ≤10 g/dl; group 2:Hb = 10–12 g/dl; group 3:Hb ≥12 g/dl), we observed a worse prognosis in patients with lower Hb levels, too (p=0.0321).A worse outcome was observed also in the transfused population (p=0.0457). At multivariate analysis including the following factors: age, sex, histotype, pT, pN, type of surgery, hemoglobin levels and transfusions, the age of patients, pT, pN and hemoglobin levels resulted indicator of prognosis. Conclusion: Our results showed that anemia represents an important prognostic factor in resected NSCLC and correction of anemia may represent an useful strategy to improve the outcome of these patients. No significant financial relationships to disclose.
Incidence of febrile neutropenia (FN) is not altered by the day of administration of pegfilgrastim (PEG)
Authors: U. Athar, A. Rajan, A. Gajra, T. P. Lynch
Journal: Journal of Clinical Oncology (2007)

19636 Background: Chemotherapy induced neutropenia can significantly increase patient morbidity and mortality and decrease the efficacy of treatment either due to a decrease in dose density and/or dose intensity of chemotherapy. Based on small studies in breast cancer and Non-Hodgkin's Lymphoma (NHL) there is concern regarding increased risk of FN if PEG is used on the same day as chemotherapy rather than 24 hours later. In our predominantly rural elderly patient population an extra visit to the infusion area can contribute to poor compliance. Hence we retrospectively analyzed patients treated at the Syracuse VA medical center who received PEG with chemotherapy to ascertain if differences existed in the incidence of FN. Methods: All patients who received PEG with cytotoxic chemotherapy between August 2002 and July 2006 were identified from hospital pharmacy records. We analyzed this population for cancer diagnosis, type and number of chemotherapy cycles, comorbidities (diabetes and COPD), use of prior or concurrent radiation, incidence of febrile neutropenia and the day of administration of PEG (Day 1 or Day &gt;1 defined as administration of PEG 24 hours or more after chemotherapy). Results: A total of 64 patients were identified and PEG was administered with a total of 212 cycles. The mean age of our patients was 70 years and 66 (97%) were males. The most common diagnoses were NHL (42 %), small cell lung cancer (18%) and non-small cell lung cancer (14 %). Other diagnoses included Hodgkin's disease, carcinoma of unknown primary and multiple myeloma (4% each). Comorbidities included diabetes mellitus and COPD (31% each). A total of 17 patients (27%) received prior or concurrent radiation therapy. PEG was given on Day 1 with 112 cycles (53%) and on Day &gt;1 with 100 cycles (47%) of chemotherapy. FN developed with 5 of 112 (4.5%) cycles when PEG was given on day 1 and 5 of 100 (5%) cycles when given on Day &gt; 1. Conclusions: In this single institution, retrospective cohort of patients the timing of PEG administration (day 1 or &gt; 1) did not affect the incidence of FN. If confirmed in larger prospective series, then current guidelines may be altered to include PEG administration on the day of chemotherapy as an acceptable standard. This would enhance patient comfort and may improve compliance with PEG therapy. No significant financial relationships to disclose.
The mean probability of finding cancer in transrectal ultra sound guided prostate biopsy: An update
Authors: E. J. Gamito, A. Tewari, E. D. Crawford, C. R. Porter, J. Presti, C. O'Donnell, G. Bartsch, W. Horninger, H. Klocker, M. Menon
Journal: Journal of Clinical Oncology (2004)

4613 Background: We provide an update to our previously presented study resulting in a useful table that provides estimated probability of a positive transrectal ultrasound (TRUS) guided prostate biopsy based on patient age, digital rectal exam (DRE) findings, and baseline serum prostate specific antigen (PSA) level. We validated the tables with two datasets from two different institutions. Methods: A step-wise logistic regression model was developed using data from 3,814 men participating in the Tyrol Screening Project (Europe) from January 1993 to April 2001. Variables used in the model were age, DRE findings, and serum PSA level. Bootstrap validation was used and 95% confidence intervals were calculated for each mean probability estimate. The resulting model was used to generate a look up table and then validated with prospective data from 491 Virginia Mason Medical Center (VM) patients and 474 Stanford University (SU) patients. Results: In the Tyrol data used to build the base model, the mean age was 63 and mean PSA was 9.6 ng/mL. DRE was suspicious in 581 (15.2%) of men. Carcinoma was confirmed by biopsy in 1,022 (26.8%) men. The model achieved an area under the receiver operating characteristic curve of 0.68 on the VM data and 0.63 on the SU data. At a 90% sensitivity, the model had a specificity of 12% and 10% for the VM and SU validations, respectively. Conclusions: We have developed a simple look-up table from a large screening database that provides estimates of the probability of finding cancer by TRUS guided biopsy utilizing readily available clinical variables that is validated on two independent data sets. Such a table can be used by practitioners and patients when assessing diagnostic options for suspected cancer of the prostate. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Institute for Clinical Research, Veterans Affairs Medical Center
Advanced, unresectable hepatocellular carcinoma (HCC): responses and long-term survival after 90Yttrium microspheres (Therasphere) treatment in 80 patients
Authors: B. I. Carr
Journal: Journal of Clinical Oncology (2004)

4085 Background: The tumor responses, long-term survivals and toxicities are reported for a large group of U.S. patients (pts) with unresectable, multifocal, and bilobar HCC, treated with 90Yttrium microspheres. All pts had biopsy-proven HCC, a bilirubin of < 2.5 mg/dL and no metastases. 80 % had cirrhosis. Results: 65 pts are available for evaluation and follow-up > 1 year. 18 had PR, 24 had minor response, 19 had stable disease and 13 progressed (52.5 % responding). Responses by CT provided an underestimate of actual benefit, since 80 % of pts had major decrease in tumor vascularity by CT. Survivals were: Okuda I: median = 628 days; Okuda II: median 281 days; CLIP 0: median 812 days; CLIP 1–2: median 384 days; CLIP > 2: median 194 days. These results were remarkable since 70 % of pts required one treatment cycle ever, 26 % had two cycles, and 3 % of pts had three treatment cycles. The mean liver dose of radiation actually delivered was 145 Gy, after a typical 5 or 10 GBq dose. Main clinical toxicities were episodic nausea and abdominal pain and fatigue. There were essentially no myelo-toxicities. Bilirubin increased by 100–150 % in 24 % of pts, 150–200 % in 15 % of pts, and > 200 % in 38 % of pts. Remarkably, lymphocytes decreased in 89 % of pts, often by > 70 % over many months. There were no clinical consequences of this. Conclusions: 90Yttrium microspheres (Therasphere) appears to represent a major new nontoxic treatment for advanced-stage HCC, which is the most common form in the U.S. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MDS Nordion
Spliceosome Mediated RNA Trans-Splicing for Targeting Kappa+ B-Cell Neoplasms
Authors: Lukas Weiss, Christina Gruber, Ulrich Koller, Josefina Piñón-Hofbauer, Stefan Hainzl, Clemens Hufnagl, Thomas Melchardt, Gabriele Brachtl, Richard Greil, Johann Bauer, Alexander Egle
Journal: Blood (2014)
A randomized phase II trial evaluating safety and efficacy of an experimental chemotherapy regimen (CPT-11 + oxaliplatin [IRINOX]) and two standard arms (LV5-FU2 + CPT-11 [FOLFIRI], LV5-FU2 + oxaliplatin [FOLFOX]) in first line metastatic colorectal cancer (MCRC) (FNCLCC Accord 08)
Authors: Y. Becouarn, M. Ychou, E. Boucher, A. Adenis, L. Cany, J. Jacob, F. Cvitkovic, S. Thezenas, C. Montoto-Grillot
Journal: Journal of Clinical Oncology (2006)

3586 Background: LV5-FU2 + CPT-11 or oxaliplatin (OHP) are standard therapies in first line MCRC. This phase II trial evaluates an experimental regimen of CPT-11 + oxaliplatin, without 5FU. Methods: First line MCRC evaluable patients (pts) were randomized to receive, every two weeks, either: Arm A = OHP 85 mg/m 2 d1 followed by CPT-11 180 mg/m 2 (IRINOX), or Arm B = simplified LV5-FU2 (leucovorin 200 mg/m 2 as a 2 h-infusion d1, 5FU bolus 400 mg/m 2 d1, and 5FU continuous infusion 2400 mg/m 2 d1–2) and CPT-11 180 mg/m 2 d1 (FOLFIRI), or simplified LV5-FU2 and OHP 85 mg/m 2 d1 (FOLFOX). Results were combined for the two standard arms (FOLFIRI + FOLFOX). Results: 80 pts were included between 09/2002 and 04/2005, 40 in IRINOX (arm A), 20 each in FOLFIRI and FOLFOX (arm B). Pts characteristics (A:B): M/F = 27/13:29/11; median age (range): 63 (41–76):61 (47–75); PS (0/1/2): 16/21/3:16/22/2; median number of cycles (range): 8.0 (1–16):12 (1–26). Safety data: no toxic death. IRINOX (318 cycles): NCI G3–4 neutropenia, 43.6% (pts), 14.7% (cycles); G3–4 neurotoxicity, 17.9% (pts), 5.0% (cycles); G3–4 diarrhea, 33.3% (pts), 5.3% (cycles). FOLFIRI (238 cycles) and FOLFOX (186 cycles): G3–4 neutropenia, 40% (pts) and 23.8% (pts) respectively (8.8% and 7.6% of cycles); G3–4 neurotoxicity, 0% and 14.3% (pts), 0% and 2.7% (cycles); G3–4 diarrhea 15% and 0% (pts), 2.1% and 0% (cycles). Median relative dose-intensity was 0.86 (0.57–1.0) for CPT-11, 0.86 (0.57 -1.0) for OHP in the IRINOX arm. We observed 21 PR in the IRINOX arm, 19 PR and 2 CR in the 2 control arms, for an ORR = 52.5%, 90% CI (38–66). Median follow-up: 17 months, median PFS for IRINOX: 8.4 months. Conclusions: The combination of CPT-11 and OHP (IRINOX) at these doses, every 2 weeks, appears safe and active in first line MCRC. [Table: see text]
The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model
Authors: Jeanette Birnbaum, Vijayakrishna K. Gadi, Elan Markowitz, Ruth Etzioni
Journal: Annals of Internal Medicine (2016)

Background: Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown. Objective: To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments. Design: Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but reflecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status). Data Sources: Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry. Target Population: U.S. women aged 50 to 74 years. Time Horizon: 10 and 25 years. Perspective: Population. Intervention: Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab. Outcome Measures: Breast cancer mortality rate ratio (MRR) and absolute risk reduction (ARR) obtained by the difference in cumulative breast cancer mortality between control and screening groups. Results of Base-Case Analysis: At 10 years, screening in a 1975 trial yielded an MRR of 90% and an ARR of 5 deaths per 10 000 women. A 2015 screening trial yielded a 10-year MRR of 90% and an ARR of 3 deaths per 10 000 women. Results of Sensitivity Analysis: Greater reductions in advanced-stage disease yielded a greater screening effect, but MRRs remained similar across trials. However, ARRs were consistently lower under contemporary treatments. When contemporary treatments were available only for early-stage cases, the MRR was 88%. Limitation: Disease models simplify reality and cannot capture all breast cancer subtypes. Conclusion: Advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival. Primary Funding Source: University of Washington and National Cancer Institute.
Serum VEGF and COX-2/5LOX inhibition in advanced non-small cell lung cancer: Cancer and Leukemia Group B 150304.
Authors: M. J. Edelman, L. Hodgson, X. F. Wang, R. Christenson, E. E. Vokes, R. A. Kratzke
Journal: Journal of Clinical Oncology (2010)

7614 Background: Eicosanoids, including PGE-2 and 5-HETE, can increase blood levels of vascular endothelial growth factor (VEGF). Overexpression of COX-2 or 5-LOX increases levels of PGE-2 and 5-HETE, respectively. Elevated levels of VEGF are common in patients with non- small cell lung cancer (NSCLC). We prospectively measured VEGF in serum collected from patients enrolled in Cancer and Leukemia Group B 30203 (J Clin Oncol, 26:848-55, 2008), a randomized phase II study of eicosanoid modulation in addition to chemotherapy in patients with advanced NSCLC, to determine whether these levels had prognostic or predictive significance and whether they correlated with COX-2 expression and/or responded to inhibition of COX-2 or 5-LOX. Methods: Pre and post-treatment serum was collected from patients enrolled in CALGB 30203. Serum VEGF levels were determined using ELISA (R&D Systems). Pretreatment formalin fixed tissue was stained for 5-LOX (clone 33, BD Transduction Labs) and COX-2 (clone SP21, LabVision Corp) by immunohistochemistry. Results: Eighty eight patients with blood specimens from CALGB 30203 were included in analysis. The median baseline VEGF level was 502 pg/mL (range 55-3453 pg/ml). Dichotomized serum VEGF levels at the median inversely correlated with survival time (log rank test, p = 0.008), as did VEGF levels as a continuous explanatory variable (Wald test, p = 0.042) in a Cox regression model adjusting for age. VEGF levels were not significantly correlated with baseline COX-2 expression (Pearson r = 0.1127, p = 0.417), nor with 5-LOX expression. Treatment with COX-2 or 5-LOX inhibitors did not alter the levels. Conclusions: These data indicate that elevated serum VEGF is a negative prognostic variable in NSCLC. VEGF levels are not correlated with baseline tumor COX-2 expression, nor do they respond to COX-2 and/or 5-LOX inhibition plus chemotherapy. No significant financial relationships to disclose.
Adipose Tissue Content of Marine N-3 Polyunsaturated Fatty Acids Is Inversely Associated With Myocardial Infarction
Authors: Anders Gammelmark, Michael S. Nielsen, Christian S. Bork, Søren Lundbye-Christensen, Anne Tjønneland, Kim Overvad, Erik B. Schmidt
Journal: Journal of the American College of Cardiology (2016)
Abstract 18043: P38 MAP Kinase Negatively Regulates the Slow Force Response to Myocardial Stretch by Affecting NHE1 Phosphorylation
Authors: María C Villa-Abrille, Romina G Díaz, Maite Zavala, Irene L Ennis, Néstor G Pérez, Horacio E Cingolani
Journal: Circulation (2013)

Mechanical stretch is an important physiological and pathological stimulus to the heart. Stretch induces a biphasic increase in myocardial force generation: A first phase due to the Frank-Starling mechanism, followed by a slower increase in force called slow force response (SFR). The SFR is blunted by AT1 or ETA receptor blockade, by NHE1 inhibition and by reactive oxygen species scavenging. This suggests that it is the mechanical counterpart of an autocrine/paracrine mechanism involving release of angiotensin II (AngII) and endothelin (ET) leading to redox sensitive NHE1 phosphorylation with its consequent activation. Since previous evidence indicates that p38 MAP kinase (p38) negatively regulates the AngII/ET positive inotropic effect in the heart, we hypothesized that the same mechanism would modulate the magnitude of the SFR. Isolated rat papillary muscles were stretched from 92 to 98 % of Lmax. The SFR was 117 ± 2 % of the initial rapid phase (n=6, P&lt;0.05 vs. rapid phase) and was significantly increased after p38 inhibition with 10 umol/L SB202190 (127 ± 2 %, n=6, P&lt;0.05 vs. control SFR), indicating that p38 negatively regulates the SFR development. Since we previously demonstrated that NHE1 activation is a key factor in the chain of events leading to the SFR, we hypothesized that p38 may be modulating NHE1 activity. As an initial approach, we explored the effect of SB202190 on NHE1 activity after an acidic load (ammonium prepulse) in the absence of bicarbonate. p38 inhibition significantly increased maximal NHE1-mediated proton efflux detected at the onset of the acidic recovery [JH+ (mmol/L/min): 2.35 ± 0.25 (n=5) vs. 3.70 ± 0.39 (n=4), P&lt;0.05]. Consistently, under p38 inhibition myocardial stretch promoted a greater increase in ERK1/2 [in % of non stretched control: 166.26 ± 16.35 (stretch, n=3) vs. 231.74 ± 13.70 (strech+SB202190, n=3), P&lt;0.05], and NHE1 [in % of non stretched control: 119 ± 2 (stretch, n=4) vs. 148 ± 9 (strech+SB202190, n=4), P&lt;0.05] phosphorylation. Our results suggest that under physiological conditions p38 activation after myocardial stretch limits the increase in force during the SFR thorough a mechanism that modulates NHE1 phosphorylation.
Cluster of HIV Infections Attributed to Unsafe Injection Practices — Cambodia, December 1, 2014–February 28, 2015
Authors: Mean Chhi Vun, Romeo R. Galang, Masami Fujita, William Killam, Runa Gokhale, John Pitman, Dejana Selenic, Sovatha Mam, Chandara Mom, Didier Fontenille, Francois Rouet, Saphonn Vonthanak
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

In December 2014, local health authorities in Battambang province in northwest Cambodia reported 30 cases of human immunodeficiency virus (HIV) infection in a rural commune (district subdivision) where only four cases had been reported during the preceding year. The majority of cases occurred in residents of Roka commune. The Cambodian National Center for HIV/AIDS (acquired immunodeficiency syndrome), Dermatology and Sexually Transmitted Diseases (NCHADS) investigated the outbreak in collaboration with the University of Health Sciences in Phnom Penh and members of the Roka Cluster Investigation Team. By February 28, 2015, NCHADS had confirmed 242 cases of HIV infection among the 8,893 commune residents, an infection rate of 2.7%. Molecular investigation of the HIV strains present in this outbreak indicated that the majority of cases were linked to a single HIV strain that spread quickly within this community. An NCHADS case-control study identified medical injections and infusions as the most likely modes of transmission. In response to this outbreak, the Government of Cambodia has taken measures to encourage safe injection practices by licensed medical professionals, ban unlicensed medical practitioners, increase local capacity for HIV testing and counseling, and expand access to HIV treatment in Battambang province. Measures to reduce the demand for unnecessary medical injections and the provision of unsafe injections are needed. Estimates of national HIV incidence and prevalence might need to be adjusted to account for unsafe injection as a risk exposure.
Activated Thyroid Hormone Promotes Differentiation and Chemotherapeutic Sensitization of Colorectal Cancer Stem Cells by Regulating Wnt and BMP4 Signaling
Authors: Veronica Catalano, Monica Dentice, Raffaele Ambrosio, Cristina Luongo, Rosachiara Carollo, Antonina Benfante, Matilde Todaro, Giorgio Stassi, Domenico Salvatore
Journal: Cancer Research (2015)

Abstract Thyroid hormone is a pleiotropic factor that controls many cellular processes in multiple cell types such as cancer stem cells (CSC). Thyroid hormone concentrations in the blood are stable, but the action of the deiodinases (D2–D3) provides cell-specific regulation of thyroid hormone activity. Deregulation of deiodinase function and thyroid hormone status has been implicated in tumorigenesis. Therefore, we investigated the role of thyroid hormone metabolism and signaling in colorectal CSCs (CR-CSC), where deiodinases control cell division and chemosensitivity. We found that increased intracellular thyroid hormone concentration through D3 depletion induced cell differentiation and sharply mitigated tumor formation. Upregulated BMP4 expression and concomitantly attenuated Wnt signaling accompanied these effects. Furthermore, we demonstrate that BMP4 is a direct thyroid hormone target and is involved in a positive autoregulatory feedback loop that modulates thyroid hormone signaling. Collectively, our findings highlight a cell-autonomous metabolic mechanism by which CR-CSCs exploit thyroid hormone signaling to facilitate their self-renewal potential and suggest that drug-induced cell differentiation may represent a promising therapy for preventing CSC expansion and tumor progression. Cancer Res; 76(5); 1237–44. ©2015 AACR.