tbuckley/cabot-search huggingface dataset:
A randomized comparison of single-agent doxorubicin and epirubicin as first-line cytotoxic therapy in advanced breast cancer.
Authors: D J Perez, V J Harvey, B A Robinson, C H Atkinson, P J Dady, A R Kirk, B D Evans, P J Chapman
Journal: Journal of Clinical Oncology (1991)

One hundred forty-one patients with advanced breast cancer who had not received prior chemotherapy were randomly assigned to receive doxorubicin 60 mg/m2 or epirubicin 90 mg/m2 every 3 weeks. These doses were selected to produce equivalent toxicities. All patients were assessed for toxicity, and 138 patients were assessable for response. After a median of five treatment cycles, 47% (32 of 68) of doxorubicin-treated patients achieved a partial or complete response. Response duration and survival were 10 and 12 months for doxorubicin and 8 and 10 months for epirubicin, respectively. Noncardiac toxicities were similar for both drugs. Of 41 patients receiving doxorubicin who had serial left ventricular ejection fraction assessments, seven sustained a fall of 10% or more, and one patient developed congestive cardiac failure at a cumulative doxorubicin dose of 489 mg/m2. Of 39 patients receiving epirubicin who had serial cardiac assessments, five sustained left ventricular ejection fraction falls of 10% or more and two patients developed congestive cardiac failure at cumulative doses of 178 mg/m2 and 833 mg/m2. These data indicate that an epirubicin dose of 90 mg/m2 produces toxicity equivalent to doxorubicin 60 mg/m2 but does not improve response rates, response duration, or survival in advanced breast cancer.
Abstract 14666: Prediction of Mode of Death in Patients with Chronic Heart Failure by Cardiac I-123 Metaiodobenzylguanidine Imaging and 6- Minute Walk Test: A Long-Term Follow-Up Comparative Study
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takashi Naito, Tadao Fujimoto, Kentaro Ozu, Takumi Kondou, Kaoruko Sengoku, Hironori Yamamoto, Tsutomu Kawai, Satoshi Takahashi, Masatake Fukunami
Journal: Circulation (2012)

Background: The 6-minute walk test (6MWT) and cardiac I-123 metaiodobenzylguanidine (MIBG) imaging provide prognostic information in patients with chronic heart failure (CHF). Prediction of mode of...
Subclinical hemostatic activation and surgical volume predict peri-operative bleeding with radical prostatectomy
Authors: S. T. Tagawa, T. B. Dorff, L. Rochanda, W. Ye, D. Hannoun, N. Eiseler, G. Lieskovsky, D. G. Skinner, H. A. Liebman, D. I. Quinn
Journal: Journal of Clinical Oncology (2007)

5136 Background: Subclinical activation of hemostasis and fibrinolysis is common in cancer and has been linked with outcome. We have previously presented (2007 Prostate Cancer Symposium) preliminary data on the relationship of laboratory markers to age and prognostic variables. We now expand our report on peri-operative (op) complication implications in early prostate cancer. Methods: With IRB approval and informed consent, blood was collected prior to open radical retropubic prostatectomy with lymph node dissection. Pre-op therapy, thrombosis, and anticoagulation were exclusion criteria. Plasma was assayed in duplicate for D-dimer, thrombin-antithrombin complex (TAT), IL-6, and IL-8. Relationships to peri-op bleeding/thrombotic events (pre-op to POD#2 hemoglobin (Hgb) drop, estimated blood loss (EBL), transfusion, post-op thrombosis) were analyzed in univariate then multivariable linear regression. Results: 153 subjects have been analyzed. Median age was 63.1 (range 35–81), pre-op PSA was 5.92 ng/mL (0.23–26.2), and 118 (77%) were clinical stage T1c. 117 (76.5%) had disease confined to the prostate; 36 had pT3 and/or lymph node involvement. Pathologic Gleason scores were 6 or less in 68 (44.4%), 7 in 71 (46.4%), and 8 or higher in 14 (9%). Median EBL was 400 mL (range 50-3000), median Hgb drop was 3.5 g/dL (-0.1–6.6), and 8 (5.2 %) required RBC transfusion. One subject experienced a DVT. On univariate analysis, pre-op TAT (p&lt;0.001) and D-Dimer (p=0.023) levels correlated with hemoglobin drop. Platelet count, INR, and aPTT did not predict EBL nor Hgb drop. The 8 who required transfusions had lower pre-op platelet counts than those not requiring transfusion (p=0.004). Higher surgeon volume correlated with lower EBL (p&lt;0.001) and Hgb drop (p=0.002). Multivariable linear regression showed that TAT remained significantly associated with Hgb drop (p=0.008) and surgeon volume with EBL (p&lt;0.001) and Hgb drop (p=0.002). Conclusions: Pre-op activation of the hemostatic system is associated with less surgically related bleeding when assessed by objective measures, predicting drop in Hgb better than PT, aPTT, or platelet counts. Surgeon volume may also predict bleeding by subjective and objective measures. No significant financial relationships to disclose.
Increased MUC5B and carbonic anhydrase IX expression in the bronchial epithelium of COPD persistent sputum producers
Authors: Shruti Khurana, Kate Brown, Jorgen Vestbo, Jonathan Plumb, Dave Singh
Journal: European Respiratory Journal (2014)

Background:  MUC5AC and MUC5B are major mucin subtypes in the lung epithelium. Bronchial epithelial MUC5AC expression is increased in COPD patients compared to controls, while no difference has been found for MUC5B. We have investigated MUC5B expression in COPD patients with persistent sputum production, as previous studies may not have included patients with severe chronic bronchitis. We have also studied the expression of HIF-1α; this transcription factor accumulates rapidly during hypoxia and may regulate mucin expression.   Methods:  The distribution of MUC5AC, MUC5B, HIF-1α and its downstream marker CAIX in the bronchial epithelium of COPD persistent sputum producers, COPD patients without sputum production and healthy controls were analyzed by immunohistochemistry. Dimethyloxalylglycine (DMOG) was used to upregulate HIF-1α expression in bronchial epithelial cells, and subsequent changes in MUC5B expression were evaluated.   Results : MUC5B and CAIX expression in the bronchial epithelium was significantly higher in COPD persistent sputum producers compared to COPD sputum non-producers (p = 0.04 and p = 0.002), and healthy controls. MUC5AC expression was similar in COPD persistent sputum producers compared to non-producers, with higher expression in both COPD groups compared to healthy controls. CAIX expression correlated to HIF-1α expression (r = 0.85, p    Conclusion:  COPD persistent sputum producers have increased MUC5B and CAIX expression in the bronchial epithelium. HIF-1α can potentially increase MUC5B expression, implicating this hypoxia inducible transcription factor in mucus hypersecretion in COPD.
Use of immunohistochemical profiling of node-negative breast carcinomas for prediction of metastatic risk.
Authors: C. Charpin, S. Giusiano, V. Secq, X. Carcopino, L. Andrac, M. Lavaut, C. Allasia, P. Bonnier, S. Garcia, J. Iovanna
Journal: Journal of Clinical Oncology (2010)

10636 Background: Early-stage breast carcinomas particularly those with lymph node negative disease have recently increased due to screening programs. Patients with node negative breast cancer have a fairly good 10 year overall survival with locoregional treatment alone. However most of the patients are offered chemotherapy causing an important proportion of over treatment. Therefore markers identifying patients not requiring aggressive adjuvant therapy are urgently needed in order to avoid to unnecessarily expose women to potential toxicity and side effects of this treatment. In this study, we searched for a prognostic immunohistochemical signature indicative of risk of early metastasis in node-negative breast carcinomas that would be also relevant for the development of new tailored therapy. Methods: Quantitative measurements immunohistochemical expression of 64 markers (selected from literature data) using high-throughput densitometry (as continuous variables), of digitised microscopic micro-array images were correlated with clinical outcome in 667 node-negative breast carcinomas (mean follow-up 102 months). Multivariable (fractional polynomials) model of logistic regression allowed the selection of the best combination of markers (in terms of sensitivity and specificity) to predict patients' outcome without any categorisation using predefined cut-points for individual marker measurements. Results: A highly predictive ten-marker (out of 64) signature was identified comprising PI3K, pmTOR, pmapKAPk-2, SHARP-2, P21, HIF-1α, Moesin, p4EBP-1, pAKT and P27 that well classified 91.4 % of node-negative patients (specificity 90.9 %, sensitivity 93.7%, area under ROC curve 0.958) independently of estrogen receptors (ER), and progesterone receptors (PR) and HER-2 status (91.6 % well classified patients when ER, PR, HER-2 excluded). Conclusions: It is concluded that quantitative immunoprofiling of node-negative breast carcinomas is helpful in selecting patients who should not receive aggressive adjuvant chemotherapy and provides data for the development of tailored therapy. No significant financial relationships to disclose.
Pharmacokinetic (pk) and safety study of irinotecan (Ir) and capecitabine (Cp) administered on a weekly schedule
Authors: R. Gollamudi, S. D. Baker, K. K. Desai, I. Chaudhary, A. Kaubisch, F. J. Camacho, M. Einstein, G. Goldberg, S. Goel, S. Mani
Journal: Journal of Clinical Oncology (2006)

2061 Background: In vitro studies show synergy between Cp and Ir. Since both drugs are metabolized by carboxyl esterases (CE), the potential for competitive inhibition is possible. We conducted a study to identify a safe dose and potential drug-drug interactions of this combination. Methods: This was an open-label phase I dose escalation trial. Ir was given as a 30 min infusion on days 1 and 8, and Cp on days 1–14 of a 21 day cycle. Plasma for pk analyses was drawn on days 1 and 8, at 0, 15, 30, 45, 60, 90, 120, 240, 360 min, and 24 hr, for total CPT-11, SN-38, SN-38-glucuronide (G), and APC. Results: 47 patients (pt) - median age 60 (32–83) years; performance status 0–1 (96%); diagnoses- ovarian (10), breast (5), cervical (5), colorectal (10) and others (17) received 202 (median 4, range 1–18) cycles in 6 dose cohorts - Ir (mg/m 2 )/Cp (mg/m 2 /day in 2 divided doses) 75/1500, 85/1500, 85/1750, 100/1750, 100/2000, 115/2000. At the highest dose tested (115/2000), 1 of 3 pt developed grade (G) 4 neutropenia with fatal gram-negative sepsis. At dose level 5 (100/2000), 2 of 21 patients developed cycle 1 DLT - G 3 diarrhea/vomiting and G 3 diarrhea. Across all doses and patients, the G 3–4 toxicities observed were diarrhea (12 pt), vomiting (2 pt), fatigue (5 pt), hand-foot syndrome (1 pt), neutropenia (6 pt), anemia (4 pt), thrombocytopenia (2 pt) and elevation of AST/ALT (1 pt). Anti-tumor responses include partial response in 8 of 35 evaluable (23%) pts (3 breast, 4 ovarian, 1 cervical), a minimal response (1 breast), and a 90% decline in PSA (1 pt). Detailed pk analyses show that AUC (0-∞) of Ir, SN-38G, and APC were similar on days 1 and 8. However, SN-38 T max was longer on Day 8 (0.87 hr vs. 1.22 hr, p = 0.012). While SN-38 AUC (0-∞) was higher on day 1 by 45%, this was not statistically significant (p = 0.167). Conclusions: Cp results in a delayed conversion of Ir to SN-38, suggesting competitive inhibition of CE at a molecular level without clinical significance. This could portend a drug-drug interaction when Ir is combined with substrates of CE, and warrants further study. The combination of Ir and Cp is safe and well tolerated at 100/2000, and warrants further evaluation in breast, cervical, ovarian and other malignancies. [Table: see text]
Dentofacial trauma and players’ attitude towards mouthguard use in field hockey: a systematic review and meta-analysis
Authors: Strahinja Vucic, Rosalin W Drost, Edwin M Ongkosuwito, Eppo B Wolvius
Journal: British Journal of Sports Medicine (2015)

Background Dentofacial injuries are a risk while playing field hockey. Wearing mouthguards is recommended. Objective To synthesise findings on the prevalence and characteristics of dentofacial injuries sustained by field hockey players. We also investigated the prevalence of regular mouthguard use and players’ attitude towards use of mouthguard. Material and methods A literature search was performed using PubMed, EMBASE, OvidSP, Web of Science, Cochrane and Cinahl databases. Eligible studies were identified based on the title, abstract and full text of articles. If applicable, a random effects model was used to calculate the overall effect size; otherwise, pooled prevalence was reported. Results 11 studies were eligible for the analysis. The average proportion of field hockey players who had sustained at least one dentofacial injury varied from 12.7% (95% CI 8.5% to 17.0%) among junior and senior players to 45.2% (95% CI 39.3% to 51.0%) among elite players. We did not observe any significant differences with respect to gender. In the 2000s, a significantly higher proportion of players regularly wore a mouthguard, 84.5% (95% CI 69.3% to 99.7%) as compared with players 20 years ago, 31.4% (95% CI 22.7% to 40.1%). The most common complaints about the mouthguard were that it was unnecessary and uncomfortable. Conclusion Dentofacial injuries pose a serious problem in field hockey and a substantial number of players do not regularly wear a mouthguard. Greater use of mouthguards would be expected to reduce dentofacial injuries in field hockey.
Clinical characteristics and prognosis of chronic pulmonary aspergillosis
Authors: Jusang Kim, Joonghyun Ahn, Ahyoung Shin, Hwayoung Lee, Soonseok Kwon, Chihong Kim, Sunkyung Kim
Journal: European Respiratory Journal (2014)

Background : This study investigated the clinical features and progrnosis of of Chronic cavitary pulmonary aspe rgillosis (CCPA) Methods : we reviewed the medial records of the patients with positive serum Aspergilus IgG or Aspergillus Ag or Aspergillus species isolated from respiratory specimens. Results :A total of 35 patients with suspected pulmonary aspergillosis were identified,(4 ABPA, 3 CNPA, 8 IPA, 5 simple aspergilloma and 15 CCPA). 15 patients were males, median age of 57 years. 63.6% (n=7) of the patients were ever smokers. Old pulmonary tuberculosis (n=15) and emphysema (n=4) were primary underlying lung conditions. Most frequent symptom was hemoptysis, 42.9% (n=6). Comparing the asymptomatic simple aspergilloma, larger cavity size, pleural thickening, bronchiectasis, and BPF was more frequently found in chest computed tomography of CCPA. Total 8 patients (57.1%) were treated with itraconazole (100%), amphotericin B deoxycholate (12.5%) and voriconazole (37.5%) for mean 134 days and 2 had curative operations. For median 206 days follow up periods, 66.7% (n=6) had favorable responses in symptoms (44.4%) or radiologic findings (55.5%). During the treatment, serum Aspergillus IgG titer was decreased in patients with favorable responses (33.3%), whereas none with unfavorable responses or without the antifungal treatment.Conclusions :Previous pulmonary tuberculosis infection and emphysema could be the risk factors for CCPA development. We suggest that patients with simple aspergilloma who present progressive symptoms with radiological changes and high serum Aspergillus IgG titer should be considered to use antifungal agents, anticipating favorable clinical outcomes.
Thrombopoietin Analogs In ITP Patients Daily Practice: Treatment Profile, Efficacy and Safety
Authors: Maria Eva Mingot-Castellano, Dana Diaz-Canales, Fernando Fernandez-Fuertes, Maria Perera-Alvarez, Isabel Caparros-Miranda, Reyes Jimenez-Barcenas, Angeles Palomo-Bravo, Ana Isabel Heiniger Mazo, G ACC
Journal: Blood (2013)
The localization of plasminogen activator inhibitor-1 in glomerular subepithelial deposits in membranous nephropathy.
Authors: T Nakamura, N Tanaka, N Higuma, T Kazama, I Kobayashi, S Yokota
Journal: Journal of the American Society of Nephrology (1996)

In this study, the localization of plasminogen activator inhibitor-1 (PAI-1) and its association with glomerular subepithelial deposits of vitronectin (VN) in membranous nephropathy (MN) was evaluated. Renal biopsy tissue from 30 patients with MN along with specimens of normal kidney removed from six patients with renal tumors were examined for glomerular deposits of urokinase-type plasminogen activator, tissue-type plasminogen activator (t-PA), PAI-1, VN, and fibrinogen by using immunofluorescence and immunoelectron microscopic techniques. Deposits were characterized by pretreating the frozen sections with arginine, glycine, and t-PA to dissociate the VN-PAI-1 complexes, thus providing evidence of PAI-1 binding to VN. Glomeruli isolated from normal frozen kidney and from frozen kidney tissue with MN were subjected to immunoblot analysis. VN was found in the mesangial area and t-PA was observed along the capillary wall of normal glomeruli. Coarse granular deposits of VN, PAI-1, and t-PA were observed along the glomerular basement membrane in MN. Immunoelectron microscopy showed the presence of VN, PAI-1, and t-PA in the subepithelial immune deposits. Pretreating the samples with arginine decreased or abolished immunofluorescence staining for PAI-1 and t-PA, but not for VN. Pretreatment with t-PA decreased the immunofluorescence staining for PAI-1, but not for VN. Pretreatment with glycine decreased or abolished the staining for all three proteins. Immunoblot analysis revealed the presence of VN, PAI-1, t-PA, and t-PA-PAI-1 complex in glomeruli with MN as well as the presence of VN, but not of PAI-1, t-PA, or complex in the normal glomeruli. The findings from this study strongly suggest that PAI-1 was deposited in the glomeruli in MN as a result of binding to VN. Thus, VN-associated PAI-1 may injure the integrity of the fibrinolytic system in glomeruli affected by MN.
Overexpression and prevalence of molecular markers in patients with cancer of unknown primary (CUP)
Authors: A. Rashid, K. R. Hess, R. Lenzi, M. N. Raber, J. L. Abbruzzese, G. R. Varadhachary
Journal: Journal of Clinical Oncology (2005)

9683 Background: Despite extensive research on molecular markers in cancer, little is known about markers in CUP, which may be biologically distinct from other metastases. We retrospectively evaluated overexpression of 5 molecular markers in CUP. Methods: We examined 100 serial paraffin blocks from UPC pts with biopsies or resections done at UTMDACC. 76 with adequate tissue, were stained by immunohistochemistry for EGFR, VEGF-A, COX-2, c-erbB2, and c-kit. The staining intensity was graded on a four-tier scale from 0 to +3. We could estimate the proportion of marker overexpression with a margin of error (half-width of 95% CI) < 0.10. Results: Majority (75%) of tumors stained for EGFR and 49% for VEGF. 2+ or 3+ staining intensity was present in 61% of tumors for EGFR and 24% for c-erbB2. EGFR was frequently present with other marker(s), seen along with VEGF, c-erbB2 or Cox-2 in at least 30% of the pts. Out of the 10 possible triple staining combinations, only 3 were observed: EGFR/c-erbB2/VEGF (29%), EGFR/c-erbB2/Cox-2 (25%), and c-erbB2/Cox-2/VEGF (18%). Kaplan Meier survival by intensity of staining (0–3) did not show any significant trend. Putting 4 markers into a recursive partitioning analysis identified 5 groups based on expression values for EGFR, c-erbB2 and Cox2. Group 1 was all the EGFR (-) pts; group 2 was pts with EGFR expression, but not c-erbB2; group 3 pts were EGFR > 0, c-erbB2 =1+; group 4 pts were EGFR > 0, c-erbB2 > 1+ but with (-) Cox2; and group 5 pts were EGFR > 0, c-erbB2 > 1+, and Cox2 > 0. Median survival for grps 1, 2 and 4 combined (N = 44) was 12 mo. compared to 28 mo. for grps 3 +5 (N = 30) (p = 0.0079). Analysis with a Cox regression model did not yield significant survival prediction. Conclusions: This study describes expression of molecular markers in CUP. We observed interesting co-expression of markers, which may guide selection of combination targeted therapies in trials. The early indication of survival benefit in c-erbB2+ pts should be evaluated prospectively. No significant financial relationships to disclose.
Cost implications of delayed radiotherapy for early stage breast cancer
Authors: H. T. Gold, H. T. Do, A. W. Dick
Journal: Journal of Clinical Oncology (2009)

6549 Background: Delayed radiotherapy (RT) for early invasive breast cancer has been shown to increase recurrence rates, but whether it influences costs of treatment or downstream medical care is unknown. Methods: Using linked SEER-Medicare data from 1992–2005 for 5,905 women ages 66+ diagnosed with stage I breast cancer undergoing post-lumpectomy RT, we estimated mean total monthly costs paid by Medicare by phase of care (treatment, continuing, or terminal care). Continuing care covers costs after treatment including for recurrences, and terminal phase includes costs in the last 6 months of life. We evaluated whether costs were different by timely vs. delayed RT (delay = 12 weeks post-surgery, or 8 weeks post-chemotherapy) and patient characteristics including comorbidity, age, and race. Results: Mean monthly treatment costs were $427 lower for women with delayed RT (p &lt; 0.00001), but monthly continuing-care costs were $129 higher (p &lt; 0.00001). Delayed RT yielded a 26% decrease in monthly treatment costs (p &lt; 0.0001) and 20% increase in continuing-care costs (p &lt; 0.0001) in multivariable analyses, and inpatient comorbidity index&gt;1 yielded cost increases of 12% (p = 0.03) and 70% (p &lt; 0.0001) in those phases, respectively, compared to no comorbidity. Terminal phase costs were affected primarily by inpatient comorbidity index&gt;1 (86% cost increase compared to no comorbidity, p &lt; 0.0001) and black race (52% cost increase compared to white, p = 0.02), but not delayed RT. Treatment phase averaged 2.5 months longer for women with delayed RT (p &lt; 0.00001). Average post-treatment follow-up was 7 years. Conclusions: Delayed RT is associated with lower mean monthly costs for treatment but higher continuing-care phase costs, possibly due to higher recurrence rates. Treatment was longer for women with delayed RT, even if total treatment cost is the same, making the average monthly cost for delayed RT lower. Preliminary analysis suggests that total average costs through follow-up are nearly $11K higher for women experiencing delayed RT. Combined with higher recurrence rates, delayed RT likely is worse in terms of both costs and effectiveness. No significant financial relationships to disclose.
Use a gentle approach for refractory myeloma patients.
Authors: D E Bergsagel
Journal: Journal of Clinical Oncology (1988)

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.1988.6.5.757 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3284972 Use a gentle approach for refractory myeloma patients. D E BergsagelxD E BergsagelSearch for articles by this author https://doi.org/10.1200/JCO.1988.6.5.757 PDF "Use a gentle approach for refractory myeloma patients.." Journal of Clinical Oncology, 6(5), pp. 757–758© 1988 by American Society of Clinical Oncology