tbuckley/cabot-search huggingface dataset:
Serum LDH predicts response rate, response duration, and survival of patients (pts) with relapsed/refractory non-Hodgkin’s lymphoma (NHL) treated with <sup>131</sup>I-tositumomab (<sup>131</sup>I-Tab) or <sup>90</sup>Y ibritumomab tiuxetan (<sup>90</sup>Y-Iab) radioimmunotherapy (RIT)
Authors: Y. Taylor Diangi, C. Andreadis, J. Svoboda, S. D. Nasta, D. E. Tsai, S. M. Luger, E. A. Stadtmauer, L. H. Downs, S. Dadparvar, A. Alavi, S. J. Schuster
Journal: Journal of Clinical Oncology (2006)

17520 Background: Although both 131 I-Tab and 90 Y-Iab are approved for treatment of pts with relapsed or refractory low-grade, follicular, or transformed NHL, a prospective randomized comparison of these two forms of RIT has not been performed. We retrospectively reviewed our experience using either agent in pts with NHL. Methods: Sixty-one pts with NHL who were treated with a single course of 131 I-Tab (N = 22) or 90 Y-Iab (N = 39) between 1999 and 2005 were included in this analysis. The median age was 61 y (range 21–83 y) and the median number of prior therapies was 5 (range 1–13). Overall, 27 pts had indolent NHL (20 follicular grade 1/2, 4 small lymphocytic, and 3 marginal zone), while 34 pts had aggressive NHL (22 diffuse large cell, 10 mantle cell, and 2 follicular grade 3). Among pts, 75% had stage III/IV disease, 52% had an elevated serum LDH, and 38% had bulky disease (&gt;5 cm). These characteristics were similar for pts receiving either 131 I-Tab or 90 Y-Iab, with the exception of elevated serum LDH (64% vs. 33%, p = 0.02). Median follow up was 21 mos (range 3–55). Results: The overall response rate (ORR) was 44% with complete response (CR) in 21% of pts. The median time to progression (TTP) was 5 mos for all pts, 9 mos for responders, and 14 mos for CRs (range 4–55). Patients with indolent NHL had no difference in ORR, CR, or TTP from pts with aggressive NHL, but had a significantly longer OS (HR 0.37, p = 0.01). Elevated LDH was the only significant predictor of ORR (31% vs. 57%, p = 0.04). In multivariable analysis, elevated LDH was adversely associated with TTP (HR 2.0, p = 0.02) and OS (HR 2.7, p = 0.02) among both subgroups of NHL. We did not discern a difference in ORR, CR, TTP, or OS between 131 I-Tab and 90 Y-Iab, even when stratifying for serum LDH. Conclusions: RIT produced high response rates in heavily pre-treated pts with indolent or aggressive NHL. Elevated LDH is the most significant prognostic factor for ORR, TTP and OS in this population. Patients with an elevated LDH should be considered for alternative treatment approaches or clinical trials, including RIT in combination with chemotherapy or transplant. [Table: see text]
Late toxicity in head and neck cancer (H&N) patients (pts) treated with hyperfractionated (HF) or accelerated (AC) radiotherapy (RT) and chemotherapy (CT)
Authors: B. M. Roth, R. Giglio, L. Cerchietti, A. Blanco Saborio, V. Cuartero, P. Menendez, C. Pogany, E. Mickiewicz, M. R. Bonomi
Journal: Journal of Clinical Oncology (2004)

5610 Background:To assess late toxicity in H&N pts treated by HF or AC RT and CT. Methods: 122 pts were treated and followed since 7/95 to 4/03. Patient's characteristics were: M/F: 116/6, age: mean 58 (range 27–79), stage: I:2 (2%), II:7 (6.9%), III:39 (38.2%) and IV:54 (52.9%) and primary site: nasopharynx, 3 pts; oropharynx, 48 pts; oral cavity, 3 pts; paranasal sinus, 5 pts; hypopharynx,10 pts; larynx, 52 pts and lip, 1 pt. Fisty-six pts were treated for larynx preservation with HF RT (74.4 Gy; 1.2 Gy bid; 6.5 wk.), 10 of those received HF alone, 29 received neo-adjuvant CT with HF; and 17 received neo-adjuvant and concomitant CT and HF. Whereas 66 pts with locally advanced inoperable H&N were treated with AC RT (70 Gy; 1.5 Gy bid; 5 wk) and concomitant CT. The CT schedule associated with HF and AC RT was Cisplatin + 5-FU. Late toxicity was evaluated using the RTOG/EORTC morbidity scoring. Overall survival (OS) and Progression-free survival (PFS) were estimated using the Kaplan-Meier method. Results:102 pts were valuable for toxicity. The mean follow-up was 34 months (range 6–98 months). Twenty one episodes of late severe toxicity (Grade 3–4 RTOG/EORTC) were registered in 17 pts. The most common sites affected were esophagus (G3: 7 pts) and larynx (G3: 4 pts and G4: 3 pts). There were no deaths related to toxicity. No correlation between late toxicity and RT and/or CT schedule and primary site were found. The 2 year OS (n=122) was 88%. The 2 year PFS (n=122) was 76.8% (95%CI: 65–85.5%). Conclusions:HF or AC RT associated with Cisplatin + 5FU had an acceptable late toxicity and good PFS in H&N pts. No significant financial relationships to disclose.
Abstract 15813: Perioperative CK-MB Elevation is a Better Predictor of Survival Than New Q Waves Among Diabetic Patients With Multivessel Coronary Artery Disease Undergoing CABG
Authors: Michael Domanski, Michael Farkouh, Victor Zak, John Alexander, Andrzej Bochenek, Martial Hamon, Kenneth Mahaffey, John Puskas, Peter Smith, Peter Shrader, Valentin Fuster
Journal: Circulation (2013)

Background: Perioperative myocardial infarction (MI) worsens prognosis after coronary artery bypass grafting (CABG). Whether new Q waves or myocardial necrosis biomarker elevation is better to asce...
Abstract 15825: Acetylation and Methylation Modifiers Attenuate Thrombin-induced eNOS/RhoA Signaling and Restore Adherens Junction Integrity in Acute Lung Injury
Authors: Jayakumar Thangavel, Sheeja Rajasingh, Bahar Barani, Buddhadeb Dawn, Johnson Rajasingh
Journal: Circulation (2014)

Introduction:  Acute lung injury (ALI) involves severe dysregulation of the restrictive endothelial barrier with consequent fluid exudation and cellular infiltration. Targeting pathways that may restore lung microvascular endothelial barrier function may lead to new therapy for this condition.   Hypothesis:  Epigenetic modifiers TSA (Trichostatin-A, HDAC inhibitor) and Aza (5-aza-2-deoxycytidine, DNA methyl transferase inhibitor) when used together will inhibit thrombin-induced eNOS/RhoA signaling, restore adherens junction (AJ) integrity, and diminish endothelial hyperpermeability.   Methods:  Molecular signaling, AJ integrity, and endothelial permeability were assessed by quantitative RT-PCR, immunofluorescence, Western analysis, and trans-endothelial resistance (TER).   Results:  Our data show that the combination of TSA+Aza is more effective in inhibiting thrombin-induced lung hyperpermeability than TSA alone or Aza alone. We used an in vitro culture system of TER to determine the effects of TSA+Aza on thrombin-induced change in resistance over human pulmonary arterial endothelial cells. Our immunofluorescence data show that treatment with TSA+Aza ameliorates thrombin-induced endothelial barrier disruption (Figure, white arrows). The Western data show that treatment with TSA+Aza decreases the levels of thrombin-induced RhoA and eNOS signaling in lung endothelial cells.   Conclusions:  These data indicate, for the first time, that the combination of TSA+Aza exerts a protective role in preventing lung microvascular hyperpermeability and endothelial barrier disruption in thrombin-induced lung injury. This combination has therapeutic potential for acute lung injury.
Cytogenetic and molecular abnormalities in chronic myelomonocytic leukemia
Authors: M M Patnaik, A Tefferi
Journal: Blood Cancer Journal (2016)

Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder associated with peripheral blood monocytosis and an inherent tendency to transform to acute myeloid leukemia. CMML has overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Clonal cytogenetic changes are seen in ~30%, whereas gene mutations are seen in >90% of patients. Common cytogenetic abnormalities include; trisomy 8, -Y, -7/del(7q), trisomy 21 and del(20q), with the Mayo-French risk stratification effectively risk stratifying patients based on cytogenetic abnormalities. Gene mutations frequently involve epigenetic regulators (TET2 ~60%), modulators of chromatin (ASXL1 ~40%), spliceosome components (SRSF2 ~50%), transcription factors (RUNX1 ~15%) and signal pathways (RAS ~30%, CBL ~15%). Of these, thus far, only nonsense and frameshift ASXL1 mutations have been shown to negatively impact overall survival. This has resulted in the development of contemporary, molecularly integrated (inclusive of ASXL1 mutations) CMML prognostic models, including Molecular Mayo Model and the Groupe Français des Myélodysplasies model. Better understanding of the prevalent genetic and epigenetic dysregulation has resulted in emerging targeted treatment options for some patients. The development of an integrated (cytogenetic and molecular) prognostic model along with CMML-specific response assessment criteria are much needed future goals.
Risk factors for severe anemia requiring red blood cell transfusions in lymphoma patients receiving chemotherapy
Authors: X. Zhou, S. R. Teegala, A. Huen, Y. Ji, L. E. Fayad, J. E. Romaguera, F. B. Hagemeister, S. Vadhan-Raj
Journal: Journal of Clinical Oncology (2007)

19537 Background: Anemia is a frequent complication in lymphoma pts receiving chemotherapy (CT). However, the exact incidence of anemia with the current regimens and risk factors for severe anemia are not well established. Methods: A retrospective cohort study was conducted to determine the incidence of anemia requiring transfusions (Tx). Medical records of all newly referred lymphoma pts (n=1046) in 2003 were reviewed. Logistic regression analysis was performed to identify the clinical and laboratory features correlated with anemia in lymphoma pts during initial regimen received. Results: 425 pts who received ≥ 1 cycle of treatment at MDACC were included in this analysis. Median age was 57 (range 17–87) with 262 (62%) newly diagnosed. Most common first regimens were CHOP (29%), Hyper-CVAD ± Ara-c-MTX (23%), and ABVD (8%) (± rituxan- R).The total number of cycles 1638 (median 3, range, 1–10). The incidence of anemia requiring PRBC Tx was 32 % (136/425) of pts and 14% (231/1638) of cycles (median cycle-2 for Tx). The incidence of PRBC Tx ranged from 8% to 17 % in each cycle. The incidence of PRBC Tx among most common regimens were Hyper-CVAD/ Ara-c/MTX 69 %( 66/95), CHOP 23% (29/125), and ABVD 6% (2/34). In the univariate regression analysis, CT, stage, extranodal/BM involvement, histology, Hb, Ca, β2M, LDH, WBC/lymphocyte counts, were significantly associated with the Txs. Using multivariate logistic regression, baseline Hb (&lt; 12 g/dL vs. ≥ 12 g/dL: OR 2.659, 95% CI 1.670 to 4.232, p&lt; 0.0001), extra nodal involvement (± : OR 2.578, 95% CI 1.609 to 4.133, p&lt;0.0001), and CT (high vs low risk: OR 3.889, 95% CI 2.446 to 6.183, p&lt;0.0001) were the most important baseline risk factors for PRBC Txs. Conclusions: The incidence of anemia in this population is high in early cycles. Baseline pt characteristics including Hb (&lt;12g/dL), extra nodal involvement, and high risk CT were found to be significant risk factors predictive for anemia and Txs. These findings could be useful to identify high risk pts for consideration of prophylaxis with erythropoietic agents for prevention of anemia. No significant financial relationships to disclose.
Abstract 14142: Association between Myocardial Triglyceride Content and Cardiac Function in Healthy Subjects and Endurance Athletes: Assessed by 1H-Magnetic Resonance Spectroscopy and Magnetic Resonance Imaging
Authors: Eiryu Sai, Kazunori Shimada, Meangkyu Kim, Takayuki Yokoyama, Shuji Sato, Tetsuro Miyazaki, Yoshifumi Tamura, Shigeki Aoki, Hirotaka Watada, Ryuzo Kawamori, Hiroyuki Daida
Journal: Circulation (2012)

Background: Recent studies have reported that myocardial lipid content as well as skeletal muscle steatosis is associated with metabolic disorders. An athlete’s paradox in which endurance athletes have high levels of skeletal muscle lipids has been reported, however, myocardial triglyceride (MTG) content in athletes has not been investigated. Method: Proton magnetic resonance spectroscopy (1H-MRS) for measuring MTG content and cardiac magnetic resonance imaging using a 1.5T-MR scanner (Avanto, SIEMENS) were performed in 10 male athletes and 15 healthy male controls (Figure). Serum markers and other clinical parameters, including intima-media thickness and arterial stiffness were measured. Cardiopulmonary exercise testing was also performed. Result: No significant differences in clinical characteristics, including age, anthropometric parameters, blood test results, intima-media thickness, or arterial stiffness were observed between both groups. Peak oxygen uptakes, end diastolic volume (EDV), end systolic ...
Comparison of adjuvant chemotherapy use in African American women with breast cancer versus the rest of the adjuvant breast cancer population
Authors: J. M. Quigley, W. Bule, J. Runyun, A. Moseley
Journal: Journal of Clinical Oncology (2006)

6069 Background: Demographics, specifically race have been discussed as reasons for disparity of care in the breast cancer setting. Methods: We used a validated database with physician entered, de-identified patient data from a randomized sample of oncologists in the US. Physicians capture de-identified data on up to 20 patients per week using a clinically validated, software driven algorithm. We evaluated all female patient records with breast cancer that were receiving adjuvant chemotherapy for their disease, from January 2005 through November 2005. All data elements are required fields, allowing for a complete patient record with each entry, including race, age, stage, nodal status, hormone status, her 2 status and chemotherapy treatments. Results: During this 11 month period, 4465 adjuvant breast cancer records were received. All were included in this analysis. Of the 4465 patient records, 69%( n=3085) were Caucasian, 18% (n= 830) were African American, 9% (n=408) were Hispanic/Latino and 4% were ‘other, which included, Native American and Asian patients. The average age for Caucasian patients was 56 years; average age for African American patients was 55 years, average age for Hispanic/Latino patients 51 years, average for all other patients 55 years. 63% of the Caucasian patients had node + disease, 59% of African Americans had node + disease, 62% of Hispanic/Latinos had node + disease, and 61% of all others had node + disease. Top treatment regimens for Caucasian patients were AC followed by Taxol (dose dense), AC, AC followed by Taxotere (dose dense), ACT (Taxotere) and CMF. Top treatment regimens for African Americans were AC followed by Taxol (dose dense), AC, AC followed by Taxotere (dose dense), ACT (Taxotere) and FAC. Conclusions: In this clinically similar patient population there was no difference in adjuvant chemotherapy selected based upon race. Further evaluations of treatment selections, including, surgery, radiation and endocrine therapy by race are warranted. No significant financial relationships to disclose.
Evaluation of Arterial Insufficiency of the Legs: A Comparison of Arteriography and the 133Xe Walking Test
Authors: J. S. Alpert, O. A. Larsen, N. A. Lassen
Journal: Cardiovascular Research (1968)

Muscle blood flow (133Xe clearance technique) measured in the legs during walking was more effective than arteriography in the evaluation of vascular insufficiency in 31 patients with intermittent claudication. Since, moreover, the 133Xe walking test is virtually without risk to the patient, it is recommended that arteriographic studies be reserved as a pre-operative investigation.
Bortezomib induces oxidative stress and apoptosis that are synergistically enhanced by a Bcl-2 inhibitor in human pancreatic cancer cells
Authors: B. Yeung, E. N. Freeburg, D.-C. T. Huang, F. A. Sinicrope
Journal: Journal of Clinical Oncology (2005)

3161 Background: Bortezomib (Velcade) is a potent and reversible proteosome inhibitor that has shown in vitro and in vivo activity against tumor types including pancreatic cancer. Inhibition of the 26S proteosome induces apoptosis that is blocked by Bcl-2, an inhibitor of oxidative stress and mitochondrial injury. We determined the effect of a small molecule Bcl-2 inhibitor (HA14–1) plus bortezomib on mitochondrial membrane potential [delta psi(m], generation of reactive oxygen species (ROS), and apoptosis induction. Materials & Methods: BxPC-3 cells, grown in RPMI 1640 medium with 10% FBS, were incubated with bortezomib (25, 50, 100 nM), HA14–1 (15 μM) or their combination for 48 h. Sequential treatment (second drug added after 24 h) was also performed. For analysis of delta psi(m), cells (5 x 106) were incubated in dihexyloxacarbocyanine iodide [40 nM] or for ROS, in dihydroethidium (2 μM) at 37°C for 15 min. Floating and attached cells were harvested and FACS analysis was performed. Apoptosis was measured by Annexin V-FITC labeling. Bcl-2 and Bcl-xL expression were determined by immunoblotting. Results: BxPC-3 cells overexpressed Bcl-2 and Bcl-xL proteins. Incubation of these cells with bortezomib (48 hr) markedly changed mitochondrial membrane potential (delta psi(m) and generated ROS, whereas HA14–1 produced minimal changes compared to untreated cells. Co-administration or sequential treatment with bortezomib followed by HA14–1 changed delta psi(m) and generated ROS to a greater extent than did bortezomib alone or the reverse sequence. By Annexin V FITC labeling, bortezomib triggered a dose-dependent increase in apoptosis and a 3-fold increase over control cells at 100 nM. HA14–1 did not induce apoptosis over control cells. Bortezomib followed by HA14–1 induced apoptosis to a greater extent than did bortezomib alone, their co-administration, or the reverse sequence. Conclusion: Bortezomib induces oxidative stress and mitochondrial injury that are coupled with induction of apoptosis. These events were synergistically enhanced by co-administration or subsequent treatment with a Bcl-2 inhibitor, suggesting a novel therapeutic strategy against pancreatic cancer. No significant financial relationships to disclose.
Gender-related differences after two exercise training programs in patients with COPD
Authors: Gianna Waldrich Bisca, Andrea Akemi Morita, Igor Brito, Karina Couto Furlanetto, Leila Donaria, Aline Nellessen, Antenor Rodrigues, Thaís Sant'Anna, Nidia Aparecida Hernandes, Fabio Pitta
Journal: European Respiratory Journal (2014)

Background:  There are insufficient data to support or refute a relation between gender and the response to exercise training in patients with COPD.   Objective:  To investigate differences between men and women with COPD concerning the responses to two training regimens: a high-intensity endurance-and-strength training program, and a low-intensity calisthenics-and-breathing-exercises program.   Methods:  We randomized 87 patients with COPD into high-(23 men: FEV 1  42±18%pred; 22 women: FEV 1  43.2[32;63]%pred) or low-(26 men: FEV 1  39[26;48]%pred; 16 women: FEV 1  49± 14%pred) intensity exercise training (3-month duration, 3x/week). Patients underwent the following assessments pre and post-program: 6-min walk test (6MWT), body composition (FFM), inspiratory and expiratory muscle force (MIP/MEP), 1-Repetition Maximum (Quadriceps-Q, Biceps-BB and Triceps brachialis-TB) and responded to questionnaires of health-related quality of life and functional status.   Results:  No differences between men and women were observed in the two exercise training groups: high (Δ6MWT 52±39  vs  47±27m; ΔFFM -0.28±1.3  vs  0.24±1.1kg; ΔMIP 0[-5;15]  vs  5[0;11]cmH 2 O; ΔMEP -0.2±26  vs  4±20cmH 2 O; ΔQ 4[2;8]  vs  3[1;6]kg; ΔBB 4[2;6]  vs  3[2;4]kg; ΔTB: 4[2;6]  vs  4[2;5]kg) or low-intensity (Δ6MWT 30±47  vs  35±77m; ΔFFM -0.2±1.9  vs  0.7±1.5kg; ΔMIP 5[-5;11]  vs  15[1;29]cmH 2 O; ΔMEP 5[-1;10]  vs  15[0;25]cmH 2 O; ΔQ 1[0;3]  vs  2[-1;6]kg; ΔBB 1.6±2  vs  0.7±4kg; ΔTB 1[0;2]  vs  1[-1;4]kg) (p>0.05 for all). Neither quality of life nor functional status improved differently between genders ( p >0.05 for all).   Conclusion:  Regardless of whether patients with COPD performed high or low-intensity exercise training, men and women benefit similarly after the intervention.
Patient and disease characteristics of women with acute myelogenous leukemia (AML) and a history of breast cancer (BC).
Authors: R. R. Yehia, D. Rangachari, K. A. Reiss, A. Blackford, A. Bardia, H. Carraway, V. Stearns, R. J. Arceci, J. E. Karp
Journal: Journal of Clinical Oncology (2010)

6560 Background: AML has been described as a long-term complication of BC-related therapy. We conducted a cross- sectional case-control study of women with AML and a prior history of BC. We described this population with regards to patient and disease characteristics and outcomes. Methods: We identified 442 women, age 21 or older, treated for AML at the Sidney Kimmel Comprehensive Cancer Center between 2003 and 2009. Cases were compared to 120 randomly selected controls with AML and no prior history of BC. Using retrospective chart review, we analyzed patient demographics, BC characteristics and treatment, and AML characteristics and treatment. Cases and controls were compared using Fisher's exact test for categorical variables and Wilcoxon rank sum tests for continuous variables. Overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan- Meier method. Results: Of the 442 women with AML, 13% (n=59) had a prior history of BC. Of the cases, 44% (n=24) had a family history (FH) of BC and/or ovarian cancer, compared to 16% (n=16) of controls. High risk cytogenetics were identified in 55% (n=26) of cases, compared to 42% (n=40) of controls (p=0.255). Of the cases, 49% (n=29) received chemotherapy for their BC, while 15% (n=9) received surgery alone. Survival estimates for women with and without BC are described in the Table. 26% (n=13) of cases received standard AML induction chemotherapy with 7+3, compared to 21% (n=24) of controls. 42% (n=21) of cases received time sequential chemotherapy (TST), compared to 35% (n=40) of controls. One-year DFS for cases was 0% for 7+3, compared to 48% for TST (p=0.013). Conclusions: There may be an increased occurrence of AML with high risk cytogenetics in women with a prior history of BC, independent of cytotoxic treatment for BC. Given the positive association with BC FH, the occurrence of AML in the setting of prior BC may relate to a unifying, underlying genetic predisposition. N Median survival (months) 1-year survival (%) Log-rank p DFS Controls 64 16.3 60 p=0.057 Cases 34 8.2 39 OS Controls 120 14.2 55 p=0.225 Cases 51 9.2 36 No significant financial relationships to disclose.