tbuckley/cabot-search huggingface dataset:
Chemotherapy in acute myelogenous leukemia: high dose, higher expectations?
Authors: E Berman
Journal: Journal of Clinical Oncology (1995)

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.1995.13.1.1 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7799008 Chemotherapy in acute myelogenous leukemia: high dose, higher expectations? E BermanxE BermanSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.1.1 First Page PDF © 1995 by American Society of Clinical Oncology
Abstract 19711: Mitochondria-Targeted Antioxidant Therapy Prevents Connexin43 Remodeling and Sudden Death Caused by Renin-Angiotensin System Activation
Authors: Ali A Sovari, Cody A Rutledge, Euy-Myoung Jeong, Elena Dolmatova, Divya Arasu, Hong Liu, Nooshin Vahdani, Lianzhi Gu, Marcelo G Bonini, Heather S Duffy
Journal: Circulation (2012)

Introduction: Previously, we showed a mouse model (ACE8/8) of cardiac renin-angiotensin system (RAS) activation has a high rate of spontaneous ventricular tachycardia (VT) and sudden cardiac death (SCD) secondary to a reduction in connexin43 (Cx43) level. Angiotensin-II activation increases reactive oxygen species (ROS) production, and these mice show cardiac oxidation. We sought to determine the source of ROS and if ROS played a role in the arrhythmogenesis. Methods and Results: Wild-type and ACE8/8 mice with and without two weeks of treatment with L-NIO (nitric oxide synthase inhibitor), sepiapterin (precursor of tetrahydrobiopterin), MitoTEMPO (mitochondria-targeted antioxidant), TEMPOL (a general antioxidant), apocynin (NADPH oxidase inhibitor), allopurinol (xanthine oxidase inhibitor), and ACE8/8 crossed with P67 dominant negative mice to inhibit the NADPH oxidase were studied. Western blotting, detection of mitochondrial ROS by MitoSOX Red, electron microscopy, immunohistochemistry, fluorescent dye diffusion technique for functional assessment of Cx43, and in-vivo electrophysiology study were performed. Treatment with MitoTEMPO reduced SCD in ACE8/8 mice (from 74% to 18%, P=0.0005), decreased VT inducibility (from 90% to 17%, P&lt;0.05), diminished elevated mitochondrial ROS to the control level, prevented structural damage to mitochondria, resulted in 2.6 fold increase in Cx43 level at the gap junctions, and corrected gap junction conduction. None of the other antioxidant therapies prevented VT and SCD in ACE8/8 mice. Conclusion: Mitochondrial oxidative stress plays a central role in angiotensin II-induced gap junction remodeling and arrhythmia. Mitochondria-targeted antioxidants may be effective antiarrhythmic drugs in cases of RAS activation.
Superoxide dismutase restores the influence of nitric oxide on renal arterioles in diabetes mellitus.
Authors: K Ohishi, P K Carmines
Journal: Journal of the American Society of Nephrology (1995)

Experiments were performed to determine the influence of endogenous nitric oxide (NO) on basal arteriolar diameter in kidneys from diabetic rats and to evaluate the role of superoxide anions as modulators of NO activity under these conditions. Male Sprague-Dawley rats were injected with streptozotocin (STZ, 65 mg/kg i.v.) and received insulin via ip osmotic minipumps (3 U/kg per day). Sham rats received vehicle treatments. Videomicroscopy was used, in conjunction with the in vitro blood-perfused juxtamedullary nephron technique, to visualize renal afferent and efferent arterioles 2 wk after the onset of diabetes. Baseline afferent arteriolar inside diameter was greater in STZ (32 +/- 2 microns) than in sham rats (24 +/- 2 microns). Efferent arteriolar diameter did not differ between STZ (24 +/- 2 microns) and sham rats (21 +/- 1 microns). In kidneys from sham rats, N omega-nitro-L-arginine (L-NNA, an NO synthase inhibitor) decreased arteriolar diameters in a concentration-dependent manner, with 100 microM L-NNA significantly reducing both afferent (13 +/- 2%) and efferent (11 +/- 1%) diameters. In kidneys from STZ rats, 100 microM L-NNA reduced afferent and efferent diameters by only 3 +/- 1 and 4 +/- 1%, respectively, indicating a suppressed arteriolar influence of NO. In STZ kidneys treated with superoxide dismutase (SOD, 150 U/mL), afferent and efferent arteriolar L-NNA responses were restored to levels comparable to those of SOD-treated and untreated sham kidneys. These observations suggest that suppressed SOD activity reduces the tonic influence of NO on renal arterioles during the early stage of diabetes mellitus, perhaps through allowing the accumulation of NO-scavenging superoxide anions.
Radiation therapy salvage of Hodgkin's disease following chemotherapy failure.
Authors: K A Fox, S M Lippman, J R Cassady, R S Heusinkveld, T P Miller
Journal: Journal of Clinical Oncology (1987)

Between 1972 and 1984, 17 patients with advanced Hodgkin's disease failing intensive combination chemotherapy in previously unirradiated nodal and/or pulmonary sites were treated with salvage radiotherapy. Treatment consisted of comprehensive wide field radiotherapy to all known areas of disease. Doses administered to these fields ranged from 1,700 to 5,000 rad, with only three patients (18%) receiving less than 3,000 rad to any field. With a median follow-up of over 4 years, 88% achieved a complete response, with median actuarial disease-free survival (DFS) of 19 months (range, 4 to 61+). Actuarial median survival was 64 months, with a range of 4 to 134+ months. Nine patients (53%) are currently alive with three (18%) in continuous complete remission (CR) for 24, 30, and 61 months. In addition, four patients relapsing after salvage radiotherapy are now in CR following additional therapy. Patients younger than 35 years of age had a significantly increased overall survival when compared with older patients (P less than .005). An initial complete response to chemotherapy lasting 12 or more months appeared to be a favorable prognostic factor, although small patient numbers preclude statistical significance. Comprehensive salvage radiotherapy is of significant benefit in patients with advanced Hodgkin's disease relapsing after combination chemotherapy in nodal and/or pulmonary sites.
The immunomodulatory effect of protein S in pulmonary fibrosis
Authors: Takehiro Takagi, Masahto Urawa, Atsushi Tomaru, Kentaro Fujiwara, Masahiro Onishi, Tetsu Kobayashi, Hiroyasu Kobayashi, Masaaki Toda, Corina D'Alessandro-Gabazza, Esteban Gabazza, Osamu Taguchi
Journal: European Respiratory Journal (2013)

Background:  Protein S (PS) is a K-dependent plasma glycoprotein with an important role in blood coagulation. PS itself may directly regulate inflammatory responses. Pulmonary fibrosis is the end stage of interstitial lung diseases that leads to a progressive loss of pulmonary function.   Objective:  This study evaluated the role of PS in pulmonary fibrosis.   Method:  Lung fibrosis was induced in wild type (WT/BLM) C57BL/6 and PS transgenic mice (PS/BLM) by bleomycin (BLM). Control groups were treated with saline (WT/SAL & PS/SAL).   Result:  WT/BLM group presented increased lung infiltration of immune cells compared to control groups and PS/BLM group. Lung collagen, hydroxyproline and plasma IL-10 levels were also significantly increased in WT/BLM compared to control and PS/BLM groups. The lung weight was significantly lower in PS/BLM group than in the WT/BLM group. The expression of the apoptosis-related markers, Casp-3 and APAF-1, was increased in the lungs of WT/BLM group compared to control and PS/BLM groups.   Conclusion:  This study showed that pulmonary fibrosis and inflammation are ameliorated in PS transgenic mice. Immunomodulatory effect of protein S may explain this protective role.
FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as initial treatment for metastatic colorectal cancer (TRIBE study): updated survival results and final molecular subgroups analyses
Authors: A. Falcone, C. Cremolini, C. Antoniotti, S. Lonardi, M. Ronzoni, A. Zaniboni, G. Tonini, L. Salvatore, G. Masi, S. Mezi, G. Tomasello, C. Carlomagno, G. Allegrini, S. Chiara, M. D'Amico, C. Granetto, C. Lupi, E. Sensi, G. Fontanini, L. Boni, F. Loupakis
Journal: Annals of Oncology (2015)
Geographic Variation in Medicare Expenditures, 2003-2012
Authors: William B. Weeks
Journal: JAMA Internal Medicine (2016)

Geographic variation in health care use and expenditures among Medicare beneficiaries has long been studied in the United States. 1 Such variation is associated with inefficiency of health care where utilization rates vary across geographic regions. 2 This variation is wasteful because higher utilization rates are not associated with better outcomes. 3One might hope that public reporting would decrease such variation.This study sought to determine whether variation in 6 cat-egories of per capita Medicare expenditures, as well as total per capita expenditures, had changed in the 10 years beginning 2003.
Phase I/II Study of Gemcitabine Plus Vinorelbine as First-Line Chemotherapy of Non–Small-Cell Lung Cancer
Authors: Vito Lorusso, Francesco Carpagnano, Giuseppe Frasci, Nicola Panza, Gaetano Di Rienzo, Mario Luigi Cisternino, Gaetano Napoli, Silvio Orlando, Saverio Cinieri, Cosimo Brunetti, Salvatore Palazzo, Mario De Lena
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the maximum-tolerated dose of gemcitabine when combined with a fixed dose of vinorelbine in the treatment of non–small-cell lung cancer (NSCLC) and to evaluate in a phase II trial the activity of this combination. PATIENTS AND METHODS: Sixty-eight patients with stage IIIB/IV NSCLC were treated with vinorelbine at fixed dose of 30 mg/m 2 intravenously and gemcitabine at increasing dose levels from 800 to 1,500 mg/m 2 intravenously on days 1 and 8 every 3 weeks. RESULTS: In phase I, dose-limiting toxicity occurred at the dosage of 1,500 mg/m 2 gemcitabine, with three of five patients developing grade 4 thrombocytopenia. In phase II, with gemcitabine at 1,200 mg/m 2 , 19 (36%) of 52 assessable patients responded. Objective response was observed in 11 (39%) of 28 patients with stage IIIB disease and in eight (33%) of 24 patients with stage IV. The median time to progression was 29 weeks (range, 2 to 41 weeks; 35 weeks and 16 weeks for stages IIIB and IV, respectively), and median survival was 54 weeks (range, 2 to 84+ weeks; 63 weeks and 42 weeks for stages IIIB and IV, respectively). One-year survival was 64% for patients with stage IIIB disease and 29% for those with stage IV. Clinical benefit response was observed in 29 (59%) of 49 assessable patients. Grade 4 leukopenia and thrombocytopenia were uncommon (6% and 8% of cases, respectively); however, grade 3/4 leukothrombocytopenia occurred more frequently in patients aged more than 70 years (52% and 24%, respectively). CONCLUSION: The combination of vinorelbine and gemcitabine is effective and tolerable in the treatment of NSCLC, thus deserving randomized trials with cisplatin combination regimens.
대한간학회 제 8 차 춘계학술대회 초록집 : 간이식 제공자의 수술 전 지방간에 대한 초음파 검사와 병리 결과의 연관성
Authors: 임재훈, 김승훈, 이순진, 이원재, 임효근, 김성현, 김수아
Journal: Clinical and Molecular Hepatology (2002)
Toxicity and one-year tumor control with induction chemotherapy and bioradiotherapy for locally advanced unresectable head and neck cancer.
Authors: C. Mercke, H. Haugen, G. Adell, F. Costa-Svedman, J. Nyman, G. Wickart-Johansson, H. Sjödin
Journal: Journal of Clinical Oncology (2010)

5581 Background: Chemoradiotherapy (CRT) and bioradiotherapy, the concurrent cytostatic component replaced by cetuximab (E) for locally advanced unresectable head and neck cancer gives similar tumor control but with less toxicity for bioradiotherapy. To reduce risk of distant metastasis and increase local efficacy, the present phase II trial explores the combination of neoadjuvant TPF and bioradiotherapy with E. Methods: Patients (pts) with untreated stage III-IV M0, WHO 0-1, unresectable squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx were scheduled for 2 cycles of TPF (docetaxel 75mg/m2 and cisplatin 75mg/m2 day 1, 5- FU 1,000mg/m2 96 hours CI) 3qw followed by RT (68Gy/4.5 weeks) with E given one week before (400mg/m2) and weekly during RT (250mg/m2). Brachytherapy of 8-15 Gy completed RT for oral and oropharyngeal tumors. Neck dissection was planned for pts with N2-3 disease. Tumor response was evaluated according to RECIST with CT, MRI or PET/CT before RT and 6 weeks follow up. Toxicity (CTC 3.0) was registered during and after treatment. Results: From 070401 to 090731 90 pts were enrolled in the study. 54 pts reached 1 year FU (study group). Median age 59, 46 males, oral cavity 5, oropharynx 30, larynx 9, hypopharynx 10, stage IV disease 53, stage III 1. Remission after TPF: CR 4, PR 30, SD 11 and PD 1, not evaluable 6, off study 2. Remission 1 year FU (evaluable pts, n=52; 2 pts denied FU) : CR 43, PR 1, SD 0, PD 0; 8 pts not evaluated regarding remission: PD 6 (dead H&N ca), intercurrent death 2 (TPF sepsis, pancreatic ca). Toxicity: Grade 5, n=1(neutropenia), grade 4, n=4/4pts (neutropenia 3, alopecia 1), grade 3, n=145/39 pts (anorexia 11/3, dermatitis 16/8, rash/acne 4/3, dysphagia 10/6, hypersensitivity 3/3 (E), mucositis 45/27, neutropenia 5/4 (chemotherapy), nausea 2/2, vomiting 2/2, infection 5/4). Vital tumor in resected specimen, n=0 /17. Tumor control 1 year FU (evaluable pts, n=52): Loco-regional 44/52 (85%), distant 51/52 (98%). Conclusions: Biotherapy with E preceded by TPF is feasible with manageable toxicities and impressive antitumor effects. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration EMD Serono
Abstract 18678: Symptoms Fail to Predict Ischemia and Cardiac Outcomes in Outpatient Diabetic Patients Referred for SPECT Myocardial Perfusion Imaging
Authors: Jamieson M Bourque, Chetan A Patel, Margarita Perez, Denny D Watson, George A Beller
Journal: Circulation (2012)

Introduction: Studies have shown a substantial prevalence of ischemic heart disease in asymptomatic diabetic patients. However, the relationship of symptoms to ischemia and events is unclear in the modern era of intensive medical management. We sought to identify the effect of symptoms on the prevalence of ischemia by SPECT myocardial perfusion imaging (MPI) and subsequent cardiac events in a cohort of outpatient, stable patients with diabetes referred for SPECT MPI. Methods: The study cohort included 575 consecutive outpatients with diabetes who underwent quantitative, gated-SPECT MPI. Data was prospectively collected and compared using Chi-Square, Kaplan-Meier, and Cox proportional hazards analyses. Results: The study population was at intermediate risk of coronary artery disease (CAD) or had known CAD (40.3%). There were no significant differences between the symptomatic patients and asymptomatic subgroup in the prevalence of ischemia (21.8% versus 22.3%, respectively, p=0.890) or significant (≥10%) left ventricular (LV) ischemia (5.1% versus 4.8%, respectively, p=0.876). Over a median 4.4 years of follow-up, the yearly rate of cardiac death/nonfatal myocardial infarction was moderate and similar between those with and without symptoms (2.3% versus 2.2%, p=0.854). Symptoms did not provide incremental prognostic benefit over clinical risk factors (p=0.230) in Cox modeling. Conclusions: The presence of symptoms failed to predict any or significant ischemia or cardiac events in a consecutive cohort of stable, outpatient diabetic patients referred for SPECT MPI. These findings highlight the need for alternative and improved risk stratification strategies in diabetic patients.
Frequency and Clinical Significance of the Expression of the Multidrug Resistance Proteins MDR1/P-Glycoprotein, MRP1, and LRP in Acute Myeloid Leukemia. A Southwest Oncology Group Study
Authors: Catherine P. Leith, Kenneth J. Kopecky, I-Ming Chen, Lisette Eijdems, Marilyn L. Slovak, Thomas S. McConnell, David R. Head, James Weick, Michael R. Grever, Frederick R. Appelbaum, Cheryl L. Willman
Journal: Blood (1999)
Genetic association analyses highlight biological pathways underlying mitral valve prolapse
Authors: Christian Dina, Nabila Bouatia-Naji, Nathan Tucker, Francesca N Delling, Katelynn Toomer, Ronen Durst, Maelle Perrocheau, Leticia Fernandez-Friera, Jorge Solis, Thierry Le Tourneau, Ming-Huei Chen, Vincent Probst, Yohan Bosse, Philippe Pibarot, Diana Zelenika, Mark Lathrop, Serge Hercberg, Ronan Roussel, Emelia J Benjamin, Fabrice Bonnet, Su Hao Lo, Elena Dolmatova, Floriane Simonet, Simon Lecointe, Florence Kyndt, Richard Redon, Hervé Le Marec, Philippe Froguel, Patrick T Ellinor, Ramachandran S Vasan, Patrick Bruneval, Roger R Markwald, Russell A Norris, David J Milan, Susan A Slaugenhaupt, Robert A Levine, Jean-Jacques Schott, Albert A Hagege, Xavier Jeunemaitre
Journal: Nature Genetics (2015)
Axitinib (AG-013736) in patients with metastatic melanoma: A phase II study
Authors: J. P. Fruehauf, J. Lutzky, D. F. McDermott, C. K. Brown, Y. K. Pithavala, P. W. Bycott, D. Shalinsky, K. F. Liau, A. Niethammer, O. Rixe
Journal: Journal of Clinical Oncology (2008)

9006 Background: No treatment has extended survival in stage IV melanoma. Melanomas are highly angiogenic and metastatic, express high levels of vascular endothelial growth factor receptors (VEGFRs) 2 and 3 and form vascular-like structures in vivo that may be exploited therapeutically. Axitinib is an oral, potent and selective inhibitor of VEGFRs 1, 2, 3 with preliminary evidence of clinical activity as monotherapy against similarly aggressive pro-angiogenic malignancies, such as metastatic renal cell carcinoma. Methods: 32 patients with ≤1 prior treatment for metastatic disease and ECOG PS 0–1 received single-agent axitinib at a starting dose of 5 mg BID. The primary endpoint was objective response rate (ORR) by RECIST criteria. BP was monitored regularly. Blood samples were also collected before and after therapy to explore pharmacodynamic (PD) and potential PK/PD relationships between clinical response and plasma soluble proteins. Results: The most common treatment-related adverse events (AEs) were fatigue (62.5%), hypertension (43.8%), hoarseness (34.4%), and diarrhea (31.3%). One patient experienced grade 5 bowel perforation. ORR was 15.6% (95% CI: 5.3, 32.8%) per investigator assessment with response duration ranging from 2.3 to >10.2 months. Median PFS was 2.3 months (95% CI: 1.8, 5.7). Median OS was 6.8 months (95% CI: 5.2, 10.4; range 0.8->22.6 months). The median OS of patients experiencing dBP ≥ 90 mm Hg on axitinib therapy was 13.0 months (n=13) vs 6.2 months for those with dBP < 90 mm Hg (n= 9). Furthermore, axitinib therapy selectively decreased soluble VEGFR2 and VEGFR3 (vs sKIT), and increased VEGF in the blood, demonstrating PD activity against the targeted VEGF receptors. The study of PK/PD relationships is ongoing. Conclusions: Axitinib has demonstrable single-agent activity in melanoma. Preliminary analyses indicate that patients who achieve elevated dBP ≥ 90 mm Hg on therapy have longer survival associated with potent and selective inhibition of targeted VEGFRs. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology Bayer, Genentech™ BioOncology, Novartis, Pfizer Oncology, Wyeth Pfizer Oncology Novartis, Pfizer Oncology Bayer, Bristol-Myers Squibb, Genentech™ BioOncology, Novartis, Pfizer Oncology, Wyeth
Radiotherapy as initial treatment for bulky stage II testicular seminomas.
Authors: S R Smalley, R G Evans, R L Richardson, G M Farrow, J D Earle
Journal: Journal of Clinical Oncology (1985)

Sixteen consecutive patients with bulky stage II seminoma were treated with primary radiotherapy from 1971 to 1982. Bulky stage II seminoma was defined as either Union Internationale Contre le Cancer (UICC) stage IIC (retroperitoneal metastases greater than 5 cm) or IID (palpable retroperitoneal metastases) with no evidence of visceral or supradiaphragmatic disease. The median age was 38 years (range, 26 to 52) and the median size of retroperitoneal disease was 11.5 cm (range, 5 to 25 cm). Patients were treated with generous radiation ports (such as wide hockey-stick or whole abdomen) often followed by boosts to the sites of bulky disease. Median tumor dose was 3,235 cGy (range, 2,700 to 5,668 cGy). Mediastinal (with or without supraclavicular) prophylactic radiation was administered to 15 of the 16 patients with a median dose of 2,590 cGy (range, 1,200 to 3,700 cGy). Treatment toxicity was mild. All 16 patients achieved a complete remission (CR) with radiotherapy. Median follow-up from the time of diagnosis was 60 months, and all patients are currently disease-free. Two patients recurred after therapy but were rendered disease-free with further radiation. These two relapsing patients have remained disease-free, following initial recurrence, for 8 years. The excellent results obtained with modern imaging and radiotherapeutic techniques justify radiotherapy as the initial treatment of choice for bulky stage II seminomas.
제10차 춘계 학술대회 초록집 : 총회구연 2 ; Lamivudine 치료로 HBeAg이 소실된 만성 B형 간염 환자에서 추가 Lamivudine 치료중의 Viral Breakthrough 발생에 관한 연구
Authors: 이지연, 유상균, 장윤정, 서연석, 연종은, 변관수, 이창홍
Journal: Clinical and Molecular Hepatology (2004)
Age-Dependent Growth Inhibition of Estrogen-Sensitive Rat Mammary Tumors. Probable Role of Alpha-Fetoprotein&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: C Sonnenschein, A A Ucci, A M Soto
Journal: JNCI Journal of the National Cancer Institute (1980)

The growth patterns of estrogen (E)-sensitive mammary tumors (SNMU) and autonomous mammary tumors (ANMU) were compared in normal host F344 and BUF rats of different ages. Both SNMU and ANMU tumors have comparable amounts of E receptors of similar physicochemical properties. The E sensitivity was apparent in SNMU tumors regardless of the age of inoculation. The latency period before tumors became palpable was considerably lengthened when the SNMU tumors were inoculated into newborn hosts. The growth pattern of the ANMU tumor was not affected by the age or sex of the host. Comparable results previously obtained with two hypophyseal cell lines suggest that this growth pattern could now be extended to other E-sensitive autonomous systems and become a generalized principle. These results suggest that: 1) the presence of 17 beta-estradiol (E2) receptors is not sufficient to qualify cells to be considered E-sensitive, 2) E-sensitive cells may be delayed in expressing their malignant growth properties if inoculated during the perinatal period, and 3) alpha-fetoprotein may be the substance responsible for the inhibition of the growth of E-sensitive tumor cells during the perinatal stage.