tbuckley/cabot-search huggingface dataset:
Evaluation of orotate phosphoribosyl transferase (OPRT), dihydropyrimidine dehydrogenase (DPD) and Thymidylate synthase (TS) in lung cancer and malignant pleural mesothelioma (MPM)
Authors: S. Matsumoto, F. Tanaka, M. Hashimoto, T. Takuwa, Y. Okumura, N. Kondo, K. Fukuoka, T. Nakano, S. Hasegawa
Journal: Journal of Clinical Oncology (2008)

22156 Background: S-1 has greater inhibition of Thymidylate synthase (TS) and Premetrexed is classified as multi-targeted antifolates. Orotate Phosphoribosyl Transferase (OPRT), Dihydropyrimidine dehydrogenase (DPD) and Thymidylate synthase (TS) are critical to the efficacy of antifolates.The difference of these enzyme activities in lung cancer and malignant pleural mesothelioma (MPM) are unknown. Methods: 83 tumor samples (65 Non-small cell lung cancer frozen tissues from patients who received thoracotomy and 18 MPM frozen tissues from patients who received biopsy or extrapleural pneumonectomy from August 2005 through October 2007). OPRT, DPD, TS were measured by ELISA. Results: In lung cancer, TS levels of tumor (30.8±56.7 ng/mg protein) were significantly different from normal tissue (2.26±2.09 ng/mg protein p=0.00005). DPD levels of tumor (437.6±237.9 ng/mg protein) and normal tissue (145.9±75.9 ng/mg protein p<0.00001), OPRT levels of tumor (3.48±2.89 ng/mg protein)and normal tissue (1.77±0.74 ng/mg protein p=0.00001)were also significantly different. Next, between lung cancer and MPM, no differences were seen in TS, DPD levels of tumor (30.8±56.7 vs. 20.7±26.2ng/mg protein, 437.6±237.9 vs. 353.8±286.3 ng/mg protein). However, OPRT level of tumor, lung cancer (3.48±2.89 ng/mg protein)was significantly increased compared to MPM(2.41±1.57 ng/mg protein p=0.02). Conclusions: We cannot find the significant differences in TS, DPD levels between lung cancer and MPM, however, OPRT level of MPM is less than lung cancer. OPRT converts 5-FU to the nucleotide form. From this study, it may suggest that efficacy of 5-FU to MPM is reduced than lung cancer. No significant financial relationships to disclose.
A phase II trial of oxaliplatin plus capecitabine (xelox) as second line therapy for patients with advanced pancreatic cancer
Authors: H. Q. Xiong, R. A. Wolff, K. R. Hess, G. R. Varadhachary, J. C. Blais, J. L. Abbruzzese
Journal: Journal of Clinical Oncology (2006)

4119 Background: There is no established chemotherapy for patients with pancreatic cancer who have progressed on gemcitabine. This trial was designed to explore the efficacy of xelox as second line therapy in patients with pancreatic cancer. Methods: The primary objective was to determine overall survival at 6 months. It was estimated that 40 patients would be needed to detect 50% 6-month survival with 90% credible interval between 37%-62%. Eligibity criteria included biopsy-confirmed diagnosis of adenocarcinoma of the pancreas, one prior systemic chemotherapy, ECOG performance status (PS) 0–2, and adequate hepatic, renal, and bone marrow functions. Oxaliplatin was administered at 130 mg/m 2 and capecitabine at 1000 mg/m 2 twice daily for 14 days for patients who were younger than 65 and had ECOG PS score 0–1. For patients older than 65 or PS 2, the oxaliplatin dose was decreased to 110 mg/m 2 and capecitabine to 750 mg/m 2 /twice daily. The treatment was repeated every 3 weeks. Tumor measurements were performed every 9 weeks (3 cycles) in patients who had measurable disease by RECIST criteria, although measurable disease was not required. Results: A total of 41 patients were enrolled into the study, 2 were never treated. Among 39 evaluable patients, 17 were female, median age 62 years (45–75), and 8 had ECOG PS 2. For the 36 patients who have completed therapy, the median number of treatment cycle was 3 (range, 1–6). Grade 3 or 4 toxicities included: abdominal pain (2 patients), dehydration (3), diarrhea (2), fatigue (6), gastrointestinal syndrome (including diarrhea and colitis) (4), hand-foot syndrome (1), hematemesis (1), mastitis (1), myocardial infarction (1), nausea/vomiting (2), neuropathy (1), non-neutropenic fever (1), pneumonia (1). One patient had a partial response and 8 others had stable disease. Median survival duration was 5.8 months (95% confidence interval [CI] 3.2–12.1 months). The six month and 1 year survival rate was 48% (95% CI 33%-70%) and 22% (95% CI 9%-51%), respectively. Conclusions: When used in the second line setting, the xelox has promising activity in pancreatic cancer. [Table: see text]
Redesigning Care for Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock
Authors: Amy G. Fiedler, Tae H. Song, David A. D’Alessandro
Journal: JAMA Surgery (2016)

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Association between feeling of well-being and overall survival in advanced lung or non-colonic gastrointestinal patients receiving palliative care.
Authors: Sriram Yennu, Yu Jung Kim, Yi Zhang, Ji Chan Park, David Hui, Duck- Hee Kang, Joseph Arthur, Gary B. Chisholm, Janet L. Williams, Suresh K. Reddy, Eduardo Bruera
Journal: Journal of Clinical Oncology (2014)

199 Background: The aim of this study was to determine the association between feeling of well-being (FWB, 0= best, 10= worst) and overall survival in advanced lung or non-colonic gastrointestinal patients who were referred to an outpatient palliative care clinic (OPC). We also determined the predictors of severity of moderate or severe - feeling of well-being in advanced lung or non-colonic gastrointestinal patients presenting to palliative care. Methods: We reviewed the records of consecutive patients with incurable advanced lung cancer and non-colonic gastrointestinal cancer presenting to OPC. Edmonton Symptom Assessment System (ESAS) scores were obtained at the initial visit between from Jan. 1, 2008-Dec. 31, 2013. Descriptive statistics were used to summarize patient characteristics. Clinically significant FWB was defined as ≥4/10. Overall Survival (OS) was calculated from the time of diagnosis of advanced cancer to death or last contact. Univariate analyses were performed and only significant variables were included in multivariate regression analysis to determine factors associated with severity OF FWB. Results: A total of 826 evaluable patients were analyzed (median age, 62 years; 57% male). Median ESAS FWB scores was 5 IQR (3-7). Worse FWB was significantly associated with OS (months) 6.33 (5.03, 8) vs 4.2 (3.37, 4.67) P=0.0003, from the time of diagnosis of advanced cancer. The final model of the Backwards Stepwise regression of factors associated with OS found that FWB (HR 1.09, p=0.3) was not an independent predictor of OS. ESAS FWB was significantly associated with ESAS fatigue (OR 2.31, p&lt;0.001); anxiety (OR 1.98, p&lt;0.001); anorexia (OR 2.31, p&lt;0.001); CAGE positivity [alcoholism] (HR 1.80, p=0.008); and family distress (HR 1.93, p=0.002). Conclusions: Worse ESAS FWB showed univariate association with OS but it does not appear to be an independent predictor of OS when controlling for other known predictors. ESAS FWB was significantly associated with fatigue, anxiety, anorexia, CAGE positivity, and family distress, suggests that ESAS FWB may be a multidimensional screening measure for patient reported health related quality of life.
Abstract 286: Survival to Hospital Discharge With Fixed 360 Joules Versus 200 Escalating to 360 Joules Defibrillation Strategies in Out-of-Hospital Cardiac Arrest of Presumed Cardiac Etiology
Authors: Jan-Aage Olsen, Cathrine Brunborg, Mikkel T Steinberg, David Persse, Chris M Souders, Fritz Sterz, Michael Lozano, Marc A Brouwer, Mark Westfall, Reinhard Malzer, Pierre M van Grunsven, David T Travis, E Brooke Lerner, Lars Wik
Journal: Circulation (2013)

Background: There is lack of evidence for fixed or escalating shock energy levels impact on survival to hospital discharge during CPR. According to the 2010 CPR consensus “maintaining the same initial energy level during subsequent shocks is acceptable. It is reasonable to increase the energy level when possible.” We studied shock success and survival to hospital discharge with fixed 360 Joules (J) versus escalating 200 to 360 J shocks, in patients in the Circulation Improving Resuscitation Care (CIRC) trial. Methods: Initial rhythm, pre-shock rhythm, rhythm 5 seconds after shock, shock energy levels and number of shocks were recorded. Patients uncategorizable as fixed or escalating shock energy protocol, without any indicated shocks or without any analyzable result from the shock were excluded from analysis. Shock success was defined as VF/VT termination at least 5 seconds after shock. Shock success between groups was calculated using chi-square test. Logistic regression determined the association between defibrillation strategy and survival to hospital discharge, after adjusting for age, initial rhythm, number of shocks, and witnessed arrests. Results: In CIRC 1657 (39%) of 4231 patients received at least one shock with analyzable defibrillator data. We included 914 fixed and 411 escalating patients. Median number of shocks per patient was 2 (IQR 1-4) in both groups. These patients received 3819 indicated shocks, 2662 in the fixed group and 1157 in the escalating group. There were 2178 (81.8%) successful shocks in the fixed group versus 963 (83.2%) in the escalating group (OR 0.91, 95% CI 0.76-1.09, p=0.29). A sub-analysis of patients whose initial rhythm was VF/VT found first shock success for 409 (83.1%) of the 492 in the fixed group versus 237 (86.5%) of the 274 in the escalating group (OR 0.77, 95% CI 0.51-1.17, p=0.22). Survival to hospital discharge for patients in the fixed group had an unadjusted OR 0.83, (95% CI 0.62-1.12, p=0.23) and adjusted OR 1.10 (95% CI 0.78-1.54, p=0.61) compared to the escalating group. Conclusion: There was no difference in individual shock success between defibrillation strategies. Further, there was no difference in patient survival to hospital discharge between the fixed versus escalating defibrillation strategies.
Overexpression of Human Stem Cell Factor Impairs Melanocyte, Mast Cell, and Thymocyte Development: A Role for Receptor Tyrosine Kinase-Mediated Mitogen Activated Protein Kinase Activation in Cell Differentiation
Authors: Reuben Kapur, Eric T. Everett, Josh Uffman, Monica McAndrews-Hill, Ryan Cooper, John Ryder, Terry Vik, David A. Williams
Journal: Blood (1997)
춘계학술대회 : 포스터전시 ; 만성 B형 간염 악화와 동반된 만성 염증성 탈수초성 다발성 신경근 신경병증 1예
Authors: 이세영, 류현욱, 엄성우, 이재현, 이명권, 김세환, 박창근, 이승엽, 김현수, 이상문, 이장준
Journal: Clinical and Molecular Hepatology (2005)

배경/목적: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)는 만성적인 진행성, 재발성 질환으로 8주 이상의 사지 허약, 심부건 반사 감소, 감각 증상 등의 임상양상을 보이며, 진단은 임상증상, 뇌척수액 검사, 신경근전도 검사 및 신경 생검으로 할 수 있다. 원인은 분명하지 않으나, 신경생검 소견 및 면역글로불린, 스테로이드 치료에 대한 반응성을 볼 때 면역기전과 관련된 신경병증으로 추
Temoporfin-mediated photodynamic therapy in advanced, incurable head and neck squamous cell carcinoma: A prospective multicenter study
Authors: I. Tan, G. Dolivet, P. Ceruse, V. Vander Poorten, P. Mahy, G. Roest, W. Rauschning
Journal: Journal of Clinical Oncology (2008)

17001 Background: To confirm the earlier reported efficacy of temoporfin-mediated photodynamic therapy (PDT) in patients with advanced, end-stage head and neck squamous cell carcinoma (HNSCC). Methods: In a prospective multicenter study, thirty-nine patients with HNSCC lesions ≤ 10 mm in depth, recurring following standard multimodality treatment, were intravenously injected with temoporfin, followed 96 hours later by illumination of the tumor surface with 652 nm laser light. Tumor response (World Health Organization criteria), quality of life (European Organization for Research and Treatment of Cancer -EORTC - Quality of Life Questionnaire QLQ-C30 and QLQ-H&N35) were assessed on an intention-to-treat basis. Treatment related toxicity (Common Toxicity Criteria - CTC) was documented rigorously. Results: 54% [95% CI: 37%; 70%] of 39 patients showed an objective tumor response (OR) and 49% [95% CI: 32%; 65%] achieved a complete response (CR; intention-to-treat analysis). Looking only at 31 evaluable patients OR was 67.7% and CR was 61.3%. At 40 weeks, a 90.5% [95% CI: 69.6%; 98.8%] survival was observed in responders as opposed to 38.9% [95% CI: 17.3%; 64.3%] for non- responders. At that point in time, between 50 and 100% of patients reported improvement in most domains of the EORTC QLQ-C30 and EORTC QLQ-H&N35. Observed treatment emergent adverse events (TEAE) were mostly cancer pain in 21% of patients, pain in general and dysphagia in 13% and phototoxicity reactions in 41%; these TEAE were mostly CTC grade 1 and 2. Conclusions: Patients with advanced HNSCC ≤ 10 mm in depth, who have exhausted other treatment options, can achieve significant local control, survival and quality of life benefit from temoporfin-mediated PDT. As opposed to conventional treatment modalities, this treatment is tolerated well. Acknowledgements: We thank the TEM-HNC-001 study group for their help and support. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Biolitec Pharma Biolitec Pharma Biolitec Pharma Biolitec Pharma Biolitec Pharma
The global burden of dengue: an analysis from the Global Burden of Disease Study 2013
Authors: Jeffrey D Stanaway, Donald S Shepard, Eduardo A Undurraga, Yara A Halasa, Luc E Coffeng, Oliver J Brady, Simon I Hay, Neeraj Bedi, Isabela M Bensenor, Carlos A Castañeda-Orjuela, Ting-Wu Chuang, Katherine B Gibney, Ziad A Memish, Anwar Rafay, Kingsley N Ukwaja, Naohiro Yonemoto, Christopher J L Murray
Journal: The Lancet Infectious Diseases (2016)
Subgroup analysis of the phase II randomized MCL-002 (SPRINT) study of lenalidomide vs investigator’s choice in relapsed/refractory mantle cell lymphoma.
Authors: Marek Trneny, Thierry Lamy, Jan Andrzej Walewski, David Belada, Jiri Mayer, John A. Radford, Wojciech Jurczak, Franck Morschhauser, Julia Alexeeva, Simon Rule, Tsvetan Nikolov Biyukov, Meera Patturajan, Marie-Laure Casadebaig Bravo, José Cabecadas, Luca Arcaini
Journal: Journal of Clinical Oncology (2015)

8547 Background: Lenalidomide, an immunomodulator with antineoplastic and antiproliferative effects, showed clinically significant improved activity over investigator choice (IC) in relapsed/refractory (R/R) MCL. This preplanned MCL-002 analysis evaluated efficacy across patient subgroups receiving lenalidomide vs IC. Methods: Patients received lenalidomide (25 mg/day PO on days 1-21/28 days) or single-agent IC therapy (chlorambucil, cytarabine, fludarabine, gemcitabine, or rituximab). The primary endpoint was progression-free survival (PFS); prespecified exploratory analyses of PFS by subgroups were conducted. Results: 254 patients with R/R MCL (median 2 prior therapies) were randomized 2:1 to lenalidomide (n = 170) or IC (n = 84). Patients receiving lenalidomide showed a significant improvement in median PFS vs IC (8.7 vs 5.2 months; HR = 0.61, P= 0.004). Subgroup analysis of PFS by central review demonstrated statistically significant reductions in the risk of progression or death in favor of lenalidomide vs IC across most baseline demographic and disease characteristics including: age ≥ 65 years, females, any stage at diagnosis, ECOG PS 0-1, both high or low tumor burden, Ki-67 < 10%, normal/elevated LDH , WBC counts < 10x109/L, no bulky disease, high MIPI score, negative bone marrow, and normal renal function. The only subgroups without risk reduction were WBC ≥ 15x109/L and positive bone marrow (both statistically insignificant), partly explained by low patient numbers in the IC arm. Risk reduction in the remaining categories was insignificant. Overall, factors associated with significantly better PFS by univariate Cox regression analysis, beside treatment group (HR = 0.619; P= 0.004), were non-elevated LDH, WBC < 10x109/L, low+intermediate MIPI, low tumor burden, and Ki-67 ≤ 30%. Highly significant in the multivariate analysis were treatment group (HR = 0.384) and Ki-67 ≤ 30% (HR = 0.344). Conclusions: Multivariate and subgroup analyses of the primary study endpoint PFS favored lenalidomide over IC therapy in providing consistent clinical benefit in patients with R/R MCL irrespective of baseline demographics or disease characteristics. Clinical trial information: NCT00875667.
Phase II study of PS-341 (bortezomib) with or without irinotecan in patients (pts) with advanced gastric adenocarcinomas (AGA)
Authors: A. J. Ocean, F. Schnoll-Sussman, R. Keresztes, X. Chen, S. Holloway, N. Matthews, P. Christos, M. Mazumdar, J. Wright, S. Wadler
Journal: Journal of Clinical Oncology (2006)

14040 Background: We are conducting a phase II trial of the proteasome inhibitor, PS-341, with or without irinotecan in pts with AGA. The combination of PS-341 and irinotecan has been studied in preclinical tumor models including a murine xenograft model of colon cancer, where the combination achieved significantly more tumor shrinkage than either agent alone. The primary objective of this study is to determine response rates, toxicities, progression-free survival, and overall survival in pts with AGA receiving PS-341 alone or in combination with irinotecan. Methods: All pts had gastric adenocarcinoma beyond the scope of surgical resection, measurable disease, and normal bone marrow, hepatic and renal function. All gave informed consent. In previously untreated patients, PS-341 was administered at 1.3 mg/m 2 on days 1, 4, 8, and 11 as IV bolus every 21 days. Irinotecan was administered IV at 125 mg/m 2 over 90 mins on days 1 and 8 every 21 days (Arm A). For previously treated patients, PS-341 was administered as a single agent at 1.3mg/m 2 on days 1, 4, 8, 11 as an IV bolus every 21 days (Arm B). Radiologic evaluation and tumor measurements were performed every 8 weeks. Results: Thirty-seven pts have been enrolled; 29 are evaluable (4 never treated, 4 TETE). Twenty-two pts were treated in Arm A, and 11 in Arm B. All pts were eligible and the 29 treated pts were fully evaluable. Median age 58 (33–87); 26 males/7 females; median number of cycles received was 2.0. Most common toxicities: Grade 4 cardiac arrest (1), stomach perforation (1), leukopenia (2), diarrhea (1), edema (1); Grade 3 nausea (6), vomiting (7), diarrhea (4), febrile neutropenia (3), thrombocytopenia (6), anemia (6); Grade 5 death (3). Severe toxicities likely attributed to disease progression. Response rate was 33% for Arm A, 9% for Arm B. Progression-free survival was 1.8 mo. in Arm A, 1.4 mo. in Arm B. Median overall survival was 4.8 mo. in Arm A, 5.4 mo. in Arm B. Conclusions: The combination of PS-341 and irinotecan, a non-cisplatin containing therapy, is active in AGA and should be considered a key regimen. Monotherapy with PS-341 has a 9% response rate in this population of pre-treated patients with advanced disease. Accrual to this study is continuing. [Table: see text]
A pilot study of AMP-224—a PD-1 inhibitor—in combination with stereotactic body radiation therapy (SBRT) in patients with metastatic colorectal cancer.
Authors: Austin G. Duffy, Oxana V. Makarova-Rusher, Suzanne Fioravanti, Melissa Walker, Aradhana Venkatesan, Nadine Abi-Jaoudeh, Bradford J. Wood, Deborah E. Citrin, Tim F. Greten
Journal: Journal of Clinical Oncology (2015)

TPS788 Background: AMP-224, a B7-DC Fc fusion protein, binds to PD-1, an inhibitory receptor that is present on the cell surface of exhausted, activated, effector, and memory T cells. AMP-224 has a unique mechanism of action in that it binds specifically to PD-1 HI T cells (chronically stimulated / exhausted T cells) but not to PD-1 LO cells which represent the normal activated T cell population. Several preclinical studies have documented an increase in peripheral antitumor immunity following radiation, a phenomenon known as the “abscopal effect”. Tumor PD-L1 expression has also been shown to be induced by radiation, which can suppress the anti-tumor immune response. Inhibition of PD-1/PDL-1 axis has been shown to improve anti-tumor immunity by blocking the tumor-mediated suppression of cytotoxic T cells. The aim of the study is to evaluate whether the anti-tumor immunity of anti-PD1 therapy (with AMP-224) can be enhanced by radiation therapy. Methods: Patients with histologically confirmed metastatic colorectal cancer to liver are being enrolled to this pilot study. The objectives are to determine the safety, tolerability and feasibility of AMP-224 in combination with stereotactic body radiation therapy (SBRT) to metastatic hepatic metastasis in patients with advanced colorectal cancer. Select eligibility are as follows: at least 1 measurable metastatic hepatic lesion by RECIST 1.1 criteria and amenable to SBRT. Patient must have progressed on or been intolerant of at least one prior oxaliplatin- and/or irinotecan-containing regimen and have metastatic lesions that are not amenable to curative resection; ECOG ≤ 1; Life expectancy of greater than 3 months. Acceptable organ and bone marrow function. No active or prior documented autoimmune or inflammatory disorders. Clinical trial information: awaited.
Effects of expiratory positive airway pressure on the electromyographic activity of accessory inspiratory muscles in chronic obstructive pulmonary disease patients
Authors: Dannuey Cardoso, Renan Jost, Andréia Paixão, Isabella Albuquerque, Dulciane Paiva
Journal: European Respiratory Journal (2011)

Background:  Chronic obstructive pulmonary disease (COPD) affect the action of the diaphragm, placing the muscle at a mechanical disadvantage and requiring the recruitment of accessory muscles of inspiration.   Objective:  To evaluate the electromyographic activity (EA) of sternocleidomastoid (SCM) and of scalene muscles during and after the use of EPAP (expiratory positive airway pressure) in COPD patients.   Methods:  A clinical single-blind trial involving 13 (57.1±7.1 years; 7M,6F) subjects with normal spirometry (controls) and 12 (57.2±8.3 years; 4M,8F) COPD patients (FEV 1  44.0±20.0%predicted; FEV1/CFV 66.8±17.4). At baseline, we determined EA during spontaneous respiration, lung function parameters, and respiratory muscle strength. Subsequently, 15 cmH 2 O EPAP was applied by face mask for 25 min, during which the EA of the SCM and scalene muscles was recorded every 5 min. A final record was obtained 10 min after the mask removal.   Results:  We found that the behavior of the EA of SCM and scalene muscles was comparable between the controls and COPD patients (p= 0.716 and p =0.789, respectively). However, during the use of EPAP, both muscles showed a trend toward an increase in the EA. In addition, there was a significant decrease in the EA of the SCM between the baseline and final measurements (p=0.034).   Conclusions:  EPAP promotes a transient increase in EA and scalene muscle SCM, suggesting that use of this modality pressure increases the activity of these muscles. However, after removal of the EA muscle SCM reduces the levels below that obtained at baseline.