tbuckley/cabot-search huggingface dataset:
Tapering oral corticosteroids in severe asthma is associated with a decrease in fractional exhaled nitric oxide
Authors: Simone Hashimoto, Anneke Ten Brinke, Jacob K. Sont, Aeilko H. Zwinderman, Peter J. Sterk, Elisabeth H. Bel
Journal: European Respiratory Journal (2011)

Rationale:  In a recent oral corticosteroid tapering study in patients with severe asthma (Hashimoto ATS 2010), we observed high levels of exhaled nitric oxide (FE NO ) despite high doses of oral corticosteroids, and, unexpectedly (Smith NEJM 2005), only a minor role of FE NO  in adjusting the dose.   Hypothesis:  Changes in FE NO  values in patients with severe prednisone-dependent asthma are not associated with changes in corticosteroid dose or clinical parameters.   Aim/Method:  48 adult patients with severe, prednisone dependent asthma (mean (SD) age 49.4 (12.2) y; 18 male) were included in this 6 months follow-up study. Relationships between changes in daily FE NO and  oral corticosteroid dose, asthma control (ACQ), and FEV 1  were assessed. Pearson correlation and regression analyses were used.   Results:  Baseline median (range) FE NO  and prednisone were 38 (5-300) pbb and 10 (0-60) mg/day. Daily changes in FE NO  from baseline were positively associated with daily changes in prednisone dose (r=0.22, p=0.003) but not with FEV 1  (r=-0.02, p=0.77) or ACQ (r=-0.03, p=0.65).   Conclusion:  In contrast to patients with mild-moderate asthma, patients with severe, prednisone dependent asthma show a decrease in FE NO  levels when prednisone is tapered.   Implication:  This suggests that oral corticosteroids may contribute to persistently high levels of FE NO  in severe asthma.
Pentostatin Therapy of T-Cell Lymphomas With Cutaneous Manifestations
Authors: Razelle Kurzrock, Susan Pilat, Madeleine Duvic
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the side effects of and response to pentostatin in patients with T-cell lymphomas with cutaneous manifestations. PATIENTS AND METHODS: Pentostatin was administered to 28 patients who had relapsed cutaneous T-cell lymphoma or peripheral T-cell lymphoma with prominent cutaneous disease. The starting dose was between 3.75 to 5.0 mg/m 2 /d intravenous for 3 days every 3 weeks. RESULTS: Of the 24 patients assessable for response, 17 (71%) achieved a partial remission (46%) or complete remission (25%). The patients had a median number of three (range, one to 12) prior therapies. Of the 86 courses of pentostatin given, 39 were administered at doses of 5.0 mg/m 2 /d and 30 at doses of 3.75 mg/m 2 /d. Dose escalation to 6.25 mg/m 2 /d was possible in only five courses, and toxicity necessitated dose reduction to 2.8 mg/m 2 /d in 12 courses. The most common side effects were granulocytopenia, nausea, and nonneutropenic fever. Most patients developed significant lowering of CD4 counts. Herpes zoster was seen within 1 year after pentostatin in five patients (19%). CONCLUSION: Pentostatin is an active agent in heavily pretreated T-cell lymphomas with cutaneous manifestations.
Phase II trial of intravenous flourouracil and subcutaneous interferon alfa-2b for biliary tract cancer.
Authors: Y Z Patt, D V Jones, A Hoque, R Lozano, A Markowitz, I Raijman, P Lynch, C Charnsangavej
Journal: Journal of Clinical Oncology (1996)

PURPOSE To assess the efficacy of systemic intravenous-fluorouracil (5-FU) and subcutaneous recombinant human interferon alfa-2b (rIFN alpha-2b) in patients with measurable cancer of the biliary tree. PATIENTS AND METHODS Thirty-five patients (25 with cholangiocarcinoma and 10 with gallbladder carcinoma) were registered onto this phase II protocol between 1992 and 1995. Patients received a continuous infusion of 750 mg/m2/d of 5-FU on days 1 through 5 through a centrally placed venous catheter and a subcutaneous injection of 5 MU/m2 of rIFN alpha-2b on days 1, 3, and 5. Treatment cycles were repeated every 14 days; one course of therapy included four treatment cycles. Disease status was assessed every 8 weeks. Dosages were lowered for grade III mucositis. Fourteen patients had prior treatment and, before initiating this therapy, 17 patients required decompression of the biliary tree. RESULTS Eleven of 32 (34%) assessable patients had a partial response. The median time to disease progression was 9.5 months, and the median survival time 12 months. Grade III to IV toxic effects were granulocytopenia (14%), mucositis (20%), diarrhea (9%), and dermatitis (11%). Grade III to IV asthenia and fatigue were observed in 6% of patients. CONCLUSION Drug tolerance was better among previously untreated patients. To achieve a complete response, additional chemotherapy or radiotherapy should be considered when liver resection or transplantation is not feasible. However, if these results can be reproduced by other investigators, the regimen should be studied for adjuvant treatment of gallbladder carcinoma incidentally identified in patients undergoing cholecystectomy.
Targeted radiopharmaceutical therapy for advanced lung cancer: Phase I trial of rhenium Re188 somatostatin analogue P2045
Authors: M. J. Edelman, G. Clamon, D. Kahn, M. Magram, B. R. Line
Journal: Journal of Clinical Oncology (2007)

7672 Background: Both small cell (SCLC) and non-small cell lung cancer (NSCLC) overexpress somatostatin receptors (SSTR). P2045 peptide is an 11-amino acid somatostatin analogue that binds with high affinity to SSTR. The analogue can be labeled with Tc-99m to gauge receptor prevalence, or with Re-188 for 2.1MeV beta radiotherapy. To evaluate the safety of this approach a phase I dose-escalation study of Re-188 P2045 in SSTR positive lung cancer was performed. Methods: Patients (pts) were required to have progressive advanced lung cancer, PS 0–1, and normal organ function. There were no limitations on the number of prior therapies. Tumor SSTR was detected with Tc-99m P2045. If positive, treatment with escalating doses of Re-188 P2045 was instituted. Three doses were evaluated, 30 mCi/m 2 , 60 mCi/m 2 and 90 mCi/m 2 . A single dose of Re-188 P2045 was allowed. Dose limiting toxicity was defined as ≥ grade 3 non-hematologic toxicity, grade 4 hematologic toxicity or projected renal radiation dose of &gt;20 Gy. Results: 15 pts entered, 7 M, 8 F, median age 61y, 9-PS0, 6 PS1. 13 NSCLC, 2 SCLC. 14 pts had ≥ 2 prior chemotherapy regimens. 1 pt refused standard therapy. All pts were imaged with Tc-99m P2045, 8 pts received Re-188 P2045. The 7 pts who did not proceed to Re-188 P2045 were due to rapid progression (n=2) non-uptake of Tc 99m P2045 (n=2) or projected renal radiation dose above the 20 Gy limit (n=3). All pts treated with Re-188 P2045 (4 at 30 mCi/m 2 , 3 at 60 mCi/m 2 and 1 at 90 mCi/m 2 ) had NSCLC. The major toxicity was grade 1 or 2 lymphopenia. No dose limiting toxicities were seen. All tumors imaged by Tc-99m had uptake of Re- 188. The trial was halted at the 90 mCi/m 2 level when 3 pts had projected renal radiation doses above 20Gy. No responses were seen. 5 of the 8 pts (62.5%, 95% CI: 24%, 91%) had stable disease at 8 weeks, all of whom entered with progressive disease.. Median overall survival was 11.5 mo. Conclusions: 1) Re-188 P2045 was well-tolerated. 2) Tc-99m P2045 imaging allows identification of pts who may benefit from Re-188 P2045. 3) While responses were not seen, survival for these heavily pretreated pts is encouraging. 4) Further exploration of this approach utilizing amino acid infusion to ameliorate potential renal toxicity is warranted. No significant financial relationships to disclose.
Targeting the WASF3–CYFIP1 Complex Using Stapled Peptides Suppresses Cancer Cell Invasion
Authors: Yong Teng, Abdulaziz Bahassan, Dayong Dong, Laura E. Hanold, Xiaoou Ren, Eileen J. Kennedy, John K. Cowell
Journal: Cancer Research (2015)

Abstract Activation of the WASF3 protein by extracellular stimuli promotes actin cytoskeleton reorganization and facilitates cancer cell invasion, whereas WASF3 depletion suppresses invasion and metastasis. In quiescent cells, the interaction between WASF3 and a complex of proteins, including CYFIP1, acts as a conformational restraint to prevent WASF3 activation. Therefore, we took advantage of this endogenous regulatory mechanism to investigate potential sites that disrupt WASF3 function. Here, we show that genetic knockdown of CYFIP1 in cancer cells led to the destabilization of the WASF3 complex, loss of WASF3 function, and suppressed invasion. Based on existing crystallographic data, we developed stapled peptides, referred to as WASF Helix Mimics (WAHM), that target an α-helical interface between WASF3 and CYFIP1. Treatment of highly invasive breast and prostate cancer cells with WAHM inhibitor peptides significantly reduced motility and invasion in vitro. Mechanistic investigations revealed that these inhibitors suppressed the interaction between Rac and the WASF3 complex, which has been shown to promote cell migration. Furthermore, peptide-mediated inhibition of WASF3 also resulted in the dysregulation of known downstream targets such as MMP-9 and KISS1. Finally, we demonstrate that this invasive phenotype is specific to WASF3 as depletion of WASF1 and WASF2, which can also bind to CYFIP1, did not affect invasion. Collectively, our findings suggest that targeting WASF3 function with WAHM peptides could represent a promising therapeutic strategy for preventing tumor invasion and metastasis. Cancer Res; 76(4); 965–73. ©2015 AACR.
Abstract P257: The Association of Metabolic Risk and Physical Activity Trajectories: CARDIA
Authors: Sarah M Camhi, Peter T Katzmarzyk, Stephanie Broyles, Timothy S Church, Arlene L Hankinson, Mercedes R Carnethon, Barbara Sternfeld, Cora E Lewis
Journal: Circulation (2012)

Purpose: To determine whether baseline metabolic risk in young adults is associated with physical activity (PA) trajectories over 20 years. Methods: The sample included young adults from the Coronary Artery Risk Development in Young Adults (CARDIA) study, baseline ages 18–30 years (n= 4161). PA was determined from self-reported questionnaire at baseline and at years 2,5,7,10,15 and 20 of follow-up. Baseline metabolic risk was calculated using age-adjusted principal components analysis (elevated=top 10% of first factor), within sex-by-race groups, from mean arterial pressure (1/3(SBP-DBP)+DBP), glucose, waist circumference, triglycerides, and high-density lipoprotein cholesterol. Repeated measures general linear modeling was used to generate PA trajectories over 20 years, separately in black men, white men, black women and white women, adjusting for age and smoking status. Time by metabolic risk interaction terms did not contribute significantly to any model for any sex-by-race group and were therefore not included in final models. Results: In black men, white men, and white women, PA (in exercise units) at baseline was significantly lower among those with elevated metabolic risk (elevated risk vs. normal risk: black men 473.0 ± 27.0 vs. 572.0 ± 22.7; white men: 498.0 ±20.6 vs. 568.7 ± 17.3; white women: 402.4 ± 17.0 vs. 481.1 ± 14.3), and these differences persisted over 20 years (black men: −98.9 ± 16.4, white men: −70.8 ± 12.5 , white women: −78.7 ± 10.2; all p&lt;0.0001). There were no significant differences in PA by metabolic risk in black women (307.2 ± 15.5 vs. 317.4 ± 13.1, difference: −10.1 ± 9.3, p =0.27). Conclusion: Elevated metabolic risk is associated with lower levels of PA in early adulthood, and these differences persist over 20 years. Despite these lower levels at baseline, the PA trajectory declines at similar rates for those with and without elevated metabolic risk. Young adults with elevated metabolic risk are important to identify early, in order to prevent PA level gap which remains over 20 years between those with and without elevated metabolic risk.
A phase II nonrandomized study of nab-paclitaxel plus carboplatin in patients with recurrent platinum-sensitive ovarian or primary peritoneal cancer.
Authors: B. B. Benigno, M. O. Burrell, P. Daugherty, P. Hernandez
Journal: Journal of Clinical Oncology (2010)

5011 Background: Paclitaxel in combination with carboplatin is effective salvage therapy for the treatment of recurrent ovarian cancer. The purpose of this study was to evaluate the antitumor activity of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin in patients with recurrent platinum-sensitive ovarian or primary peritoneal carcinoma. Methods: Patients with measurable disease received nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 of each 28-day cycle and carboplatin AUC 5 intravenously on day 1. Patients were to be treated for at least 6 cycles. Efficacy was measured by objective response rate (ORR) per RECIST, progression-free survival (PFS), and overall survival (OS). Patients were followed every 3 months for 2 years. Results: Forty eligible patients with median age of 62 years (range 43 - 81) were enrolled; 28 patients had ovarian cancer stage IIIC, 9 had stage IIB/IIIB or IIC, and 3 had stage IV disease. Most were Caucasian (83%), most had ECOG status of 0 (88%), and all had received prior taxane/platinum chemotherapies. The median (standard deviation [STDV]) platinum-free interval was 13 (8) months. The median number of cycles with nab-paclitaxel plus carboplatin was 6 (range 3-48). Of 38 patients who were evaluable (2 did not receive treatment), 15 (39%) had a complete response (CR), 15 (39%) had a partial response (PR) for an ORR of 79%. Seven (18%) patients had stable disease (SD), 1 (3%) patient had disease progression (PD). The median (STDV) PFS was 13 (11) months and median (STDV) OS was 30 (13) months. The most common grade ≥ 3 adverse events were neutropenia (43%), fatigue (33%), hypersensitivity reaction to carboplatin (18%), anemia (10%), thrombocytopenia (5%), and nausea (5%). Of the 40 patients enrolled, 11 patients have completed 2 years of follow-up, 15 patients have died, 13 patients are still being followed, and 1 patient is still receiving treatment after more than 2 years. Conclusions: With a 97% disease control rate (CR + PR + SD), the combination of nab-paclitaxel plus carboplatin had significant antitumor activity and was reasonably tolerated in patients with platinum-sensitive recurrent ovarian cancer. No significant financial relationships to disclose.
Procalcitonin-guided antibiotic use for respiratory tract infections
Authors: M Flatley
Journal: Thorax (2009)

Antibiotic therapy is widely used in primary care to treat acute respiratory tract infections in spite of predominant viral aetiology. This study investigated whether procalcitonin (PCT), a biochemical marker elevated in systemic bacterial infections, can be used to guide antibiotic treatment.

A total of 458 adults with respiratory tract infection symptoms who, in their physician’s opinion required antibiotics, …
Antigenic Characteristics of Three Variants of Rous Sarcoma Virus
Authors: P J SIMONS, R M DOUGHERTY
Journal: JNCI Journal of the National Cancer Institute (1963)

Journal Article Antigenic Characteristics of Three Variants of Rous Sarcoma Virus Get access P. J. Simons, P. J. Simons Division of Experimental Biology and Virology, Imperial Cancer Research Fund, Mill Hill, London, N.W. 7, England Search for other works by this author on: Oxford Academic PubMed Google Scholar R. M. Dougherty R. M. Dougherty Division of Experimental Biology and Virology, Imperial Cancer Research Fund, Mill Hill, London, N.W. 7, England Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 31, Issue 5, November 1963, Pages 1275–1283, https://doi.org/10.1093/jnci/31.5.1275 Published: 01 November 1963 Article history Received: 11 June 1963 Published: 01 November 1963
Late axillary recurrence after negative SLNB.
Authors: Cindy Brown Matsen, Kristine Villegas, Anne Eaton, Michelle Stempel, Aidan Manning, Monica Morrow, Alexandra S. Heerdt
Journal: Journal of Clinical Oncology (2014)

63 Background: SLNB is the standard axillary evaluation method for clinically node-negative patients with invasive breast cancer. While axillary recurrence (AR) in the early years after negative SLNB is &lt;2%, studies with longer (&gt;8 yrs) follow-up on large patient numbers are lacking. With concern that current multimodality therapy may delay time to AR, we reviewed long-term SLNB patient outcomes. Methods: We identified patients with invasive cancer from a prospective, single-institution database who had a negative SLNB without additional axillary surgery from 1/97-12/00. Cancer, demographic, and treatment data were obtained for all patients. Primary outcome was AR. Overall survival (OS) and distant disease-free survival (DDFS) after AR were secondary endpoints. Results: 1529 eligible patients were identified. See table for patient and tumor characteristics. At 10.8 yrs (0-16) median follow-up, overall incidence of AR as a first event was low, n= 13. Median OS after AR was 4.6 yrs and median DDFS after AR was 3.8 yrs. The cumulative incidence of AR was 1.0% (CI 0.5-1.6) overall; cumulative incidence of 0.6% (CI 0.2-0.9) in the first 5 years, 0.4% years 5-10. Late AR (&gt;5 yrs) occurred in 5 patients: 4 ER+, 1 HER2+. In comparison, in a group of contemporaneous SLNB-positive patients undergoing axillary dissection (n=902), overall cumulative incidence of AR was 0.8% (CI 0.2-1.5) at over 10 yrs follow-up. On univariate analysis of AR in SLNB-negative patients, high nuclear grade was the only significant predictor of AR (p=0.01). Conclusions: Late AR was an infrequent event after negative SLNB alone emphasizing its long-term safety as a staging procedure. AR after SLNB, like AR after ALND, portends a poor prognosis.[Table: see text]
Epigenetic Control of Endogenous Ecotropic Virus Expression in SL/Ni Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: H Hiai, Y O Buma, H Ikeda, K Moriwaki, Y Nishizuka
Journal: JNCI Journal of the National Cancer Institute (1987)

SL/Ni mice were found to be highly polymorphic in the expression of endogenous ecotropic virus (ETV). By selective mating of the mice with either high-virus or virus-free phenotypes, the following stably virus-positive and virus-negative sublines were obtained: SL/Ni-Eco+ and SL/Ni-Eco−, respectively. This polymorphism was produced by an epigenetic factor transmitted by SL/Ni-Eco− female mice via milk. F1 hybrids between SL/Ni-Eco− females with males of high-virus strains did not express ETV, whereas reciprocal F1 hybrids did. On the other hand, F1 mice between females of low-virus strains or of NFS mice lacking the ETV proviral genome and SL/Ni-Eco− males expressed a high level of ETV. Foster-nursing of newborn mice of high-virus strains by SL/Ni-Eco− foster-mothers or injection of pooled sera of SL/NiEco− mice resulted in intense inhibition of virus expression. On the contrary, nursing of SL/Ni-Eco− newborns by NFS/N foster-mothers resulted in high virus expression. These observations strongly support the hypothesis that failure to express ETV by SL/Ni-Eco− mice is due to a milk-transmitted maternal resistance factor, but probably not due to genetic heterogeneity among SL/Ni sublines. This factor caused strong, long-lasting, and selective suppression of endogenous ETV, but it did not confer resistance to exogenous infection of ETV. This activity was present also in the sera of SL/Ni-Eco− mice, since neonatal injection of the sera into high-virus strains of mice, SL/Ni-Eco+, SL/Kh, and AKR/Ms, caused strong selective suppression of ETV expression. By this procedure, the spontaneous occurrence of nonthymic lymphomas in SL/Kh mice was suppressed.
Impact of central pathology review (CPR) of radical prostatectomy (RP) specimens for patient selection in the surgical adjuvant trial in prostate cancer (PCa) TAX-3501
Authors: M. A. Eisenberger, M. W. Kattan, A. Kibel, C. N. Sternberg, J. Epstein
Journal: Journal of Clinical Oncology (2008)

5128 Background: Patient heterogeneity and long natural history confound the design and evaluation of clinical trials in localized PCa. Risk stratification criteria employed to select high risk patients are of limited value since the outcome after surgery is broadly variable within each risk group. While there is known inter observer variation in Gleason grading, the impact of CPR of stage and margins on eligibility for adjuvant trials remains undefined. We are prospectively evaluating a previously reported prediction tool to maximize homogeneity and targeted risk of the patient population entered in a global multi-institutional adjuvant clinical trial. Methods: TAX 3501 is a randomized post RP adjuvant trial in high risk patients comparing immediate vs. deferred androgen deprivation (AD) x18 months ± 6 cycles of docetaxel (D) q.3 wks in a 2x2 factorial design with progression free survival (PFS) as the main outcome. Eligibility included:central pathology review (Johns Hopkins ), estimated biochemical PFS of ≤ 60% based on a widely used post operative nomogram (Kattan, M et al), undetectable PSA and other conventional clinical/hematological and biochemical criteria. No radiation therapy (RT) or prior ADT was allowed. Results: The study was closed after 228 patients were randomized. Significant disagreement between local vs.central path review (196 patients) and nomogram PFS estimates (173 pts) is shown on the table below. PFS (nomogram estimates) of patients randomized is approximately 20 months which corresponds to the statistical estimates of TAX3501. Conclusions: Eligibility criteria employing central pathology review and individual patient estimates of risk of recurrence by nomogram is feasible and likely to enhance trial design and analyses. If validated with further follow up, this approach should be routinely employed in adjuvant RP studies. Supported by Sanofi-Aventis Local vs Central path review: TAX3501 Agree (%) Disagree (%) Upgraded/upstaged (more aggressive) Downgraded/staged (less aggressive) Gleason score 69 70 30 Organ confined 72 93 7 Surgical margins 90 63 37 Seminal vesicles 93 38 62 Lymph nodes 99 100 - 60% PFS on nomogram * 134 - 9 >60% PFS on nomogram 9 22 - * PFS nomogram predictions Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene, Ipsen, sanofi-aventis AstraZeneca, Ipsen, sanofi-aventis Celgene, Centocor, Cytogen, sanofi-aventis