tbuckley/cabot-search huggingface dataset:
VEGF polymorphism may be associated with overall survival in lapatinib-treated breast cancer patients with brain metastases.
Authors: Colin F. Spraggs, Li Li, Linda P. Briley, Alaknanda Joshi, Allison M. Florance, Karen King, Laura R Parham
Journal: Journal of Clinical Oncology (2012)

10532 Background: Lapatinib is a dual HER2/EGFR tyrosine kinase inhibitor (TKI) approved in combination with capecitabine or letrozole for patients with HER2+ metastatic breast cancer (MBC). Consistent with TKI therapies, patient response is variable and suggestive of additional determinants of sensitivity and resistance. This exploratory pharmacogenetic study sought to identify germline genetic variants that associate with lapatinib treatment outcomes in HER2+ MBC patients. Methods: Fifty five functional single nucleotide polymorphisms (SNPs) in 24 candidate genes were evaluated in a subset of MBC patients participating in two clinical trials: EGF105084: lapatinib monotherapy in HER2+ MBC patients with recurrent brain metastases following trastuzumab and cranial radiotherapy (n=120) and EGF104900: lapatinib plus trastuzumab (n=92) and lapatinib monotherapy (n=103) in HER2+ MBC patients with disease progression following trastuzumab. Testing for associations of SNPs with progression free survival (PFS) and overall survival (OS) during lapatinib treatment was performed using Cox proportional hazards methods, with covariate adjustment. Markers were considered to be significantly associated if they achieved a predefined multiple testing threshold of p&lt;0.0003. Results: No SNPs were significantly associated with PFS in either study. A SNP in VEGFA (rs3025039, 936C&gt;T) was significantly associated with improved OS (p=0.0002) for the T allele carriers, with an allelic hazard ratio of 0.21 (0.08-0.52) in EGF105084. The association was not seen in EGF104900. This SNP is located in the 3’ UTR gene region, the T allele is associated with lower serum VEGFA levels and reduced breast cancer risk [Krippl et al, 2003, Int J Cancer 106: 468; Kataoka et al, 2006, Cancer Epidemiol Biomarkers Prev, 15:1148]. Conclusions: A germline variant in VEGFA may be associated with survival outcome in MBC patients with brain metastases who are treated with lapatinib. This may represent activation of VEGF angiogenic pathways to overcome HER2 inhibition in patients carrying the higher expression genotype. These associations are considered exploratory and require confirmation in an independent dataset.
Clinical Management of Small-Cell Carcinoma of the Urinary Tract(SCCUT): A 10-Year Single-Center's Experience
Authors: I. Gil-Bazo, E. Castanon Alvarez, L.E. Abella, M.E. Zudaire, A. Castillo, E. Arevalo, J.P. Fusco, J.J. Zudaire, R. Martínez-Monge, O.E. Carranza
Journal: Annals of Oncology (2012)
Prophylactic fluconazole treatment of mucositis in radiotherapy of head and neck cancer patients
Authors: C. Demiroz, L. Ozkan, O. Karadag
Journal: Journal of Clinical Oncology (2009)

6062 Background: The aim of the study is to evaluate the preventive role of antifungal fluconazole prophylaxis on mucositis in head and neck cancer patients treated with radiotherapy. Methods: We evaluated 43 head and neck cancer patients treated with radiotherapy with/without chemotherapy. The patients were randomized to two groups: twenty patients (group A) received fluconazole when micotic infections appeared; 23 patients (group B) received fluconazole 200 mg once a week starting from the sixth irradiation session throughout the treatment.The two groups were similar in terms of patients and radiotherapy characteristics. Oral mucositis was recorded according to EORTC/RTOG criteria. Results: The usage of fluconazole 200 mg once a week was well tolerated and no early and late toxicity was observed. Mucositis was appeared in both groups on the third week of radiotherapy. Grade 3 mucositis developed at eight of the patients in group A (40%), three of the patients in group B (13%) and the result was statistically significant (p = 0.044). While grade 3 mucositis was observed the second/third week in group A, it was also observed in group B on third/fourth week in group B (p = 0.043). Conclusions: Weekly fluconazole prophylaxis showed a significant effect on the grade 3 mucositis and improved radiotherapy results. No significant financial relationships to disclose.
Prevention of Delayed Nausea (DN): A Pooled Analysis of 562 Women Receiving Highly Emetogenic Chemotherapy (HEC) in Prospective Clinical Trials of Palonosetron (PALO)
Authors: L. Celio, F. Longo, S. Brugnatelli, G. Mansueto, E. Bonizzoni, F.G.M. De Braud, F. Ricchini, M.S. Aapro
Journal: Annals of Oncology (2012)
P-0244 A Phase I/II Study of Tri-Weekly Xeliri Plus Bevacizumab for Japanese Patients with MCRC as Second-Line Chemotherapy (Bix Study)
Authors: Tatsuro Yamaguchi, Yasuo Hamamoto, Tomohiro Nishina, Kentaro Yamazaki, Takashi Ura, Nakajima Takako, Ayumu Goto, Ken Shimada, Norisuke Nakayama, Junichi Sakamoto, Satoshi Morita, Yasuhide Yamada
Journal: Annals of Oncology (2012)
Randomized, double‐blind, placebo‐controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA‐RESPONSE‐AHF)
Authors: Kevin Damman, Joost C. Beusekamp, Eva M. Boorsma, Henk P. Swart, Tom D.J. Smilde, Arif Elvan, J.W. Martijn van Eck, Hiddo J.L. Heerspink, Adriaan A. Voors
Journal: European Journal of Heart Failure (2020)

Abstract Aims Inhibition of sodium–glucose co‐transporter 2 (SGLT2) reduces the risk of death and heart failure (HF) admissions in patients with chronic HF. However, safety and clinical efficacy of SGLT2 inhibitors in patients with acute decompensated HF are unknown. Methods and results In this randomized, placebo‐controlled, double‐blind, parallel group, multicentre pilot study, we randomized 80 acute HF patients with and without diabetes to either empagliflozin 10 mg/day or placebo for 30 days. The primary outcomes were change in visual analogue scale (VAS) dyspnoea score, diuretic response (weight change per 40 mg furosemide), change in N‐terminal pro brain natriuretic peptide (NT‐proBNP), and length of stay. Secondary outcomes included safety and clinical endpoints. Mean age was 76 years, 33% were female, 47% had de novo HF and median NT‐proBNP was 5236 pg/mL. No difference was observed in VAS dyspnoea score, diuretic response, length of stay, or change in NT‐proBNP between empagliflozin and placebo. Empagliflozin reduced a combined endpoint of in‐hospital worsening HF, rehospitalization for HF or death at 60 days compared with placebo [4 (10%) vs. 13 (33%); P = 0.014]. Urinary output up until day 4 was significantly greater with empagliflozin vs. placebo [difference 3449 (95% confidence interval 578–6321) mL; P &lt; 0.01]. Empagliflozin was safe, well tolerated, and had no adverse effects on blood pressure or renal function. Conclusions In patients with acute HF, treatment with empagliflozin had no effect on change in VAS dyspnoea, diuretic response, NT‐proBNP, and length of hospital stay, but was safe, increased urinary output and reduced a combined endpoint of worsening HF, rehospitalization for HF or death at 60 days.
A Prospective Mono-Institutional Study on the Impact of a Systematic Prevention Program on the Incidence and Outcome of Osteonecrosis of the Jaw (ONJ) in Patients (PTS) Treated with Bisphosphonates (B) for Bone Metastases
Authors: N.M. La Verde, A. Bramati, S. Piva, M.C. Dazzani, S. Girelli, A. Moretti, D. Mihali, M. Dimaiuta, A. Pinto, G. Farina
Journal: Annals of Oncology (2012)
A Catheter‐Deployable Soft Robotic Inflatable Basket for Enhanced Conformability to the Left Atrium of the Heart
Authors: Nazanin Farokhnia, Alexandre Caprio, Varun Kashyap, Subhi Al'Aref, Lohendran Baskaran, Bobak Mosadegh, Simon Dunham
Journal: Advanced Healthcare Materials (2020)

This paper presents the design, fabrication, and test results for a novel basket catheter that utilizes soft robotic technology, which can conform to complex patient anatomy. Two designs of basket-shaped balloons in three sizes are fabricated based on a CO2 laser cutting method from thin (<50 µm) thermoplastic polyurethane. The balloons are deployed in four soft-material 3D printed left atria, whose geometries are based on volume rendered segmentation of cardiac computed tomography (CT) scans. The coverage and conformability to the realistic patient anatomies is tracked with the small patches of pH paper that indicate, via a color change, contact with a basic solution that lined the 3D printed atriums. The conformability of these inflatable basket catheters is demonstrated as high as (85%) for the optimized design. To visualize the balloon's performance, microCT images of balloons deployed in 3D printed models are shown. These images show the ability of the balloons to adapt to complex patient anatomy and do not exhibit any spline bunching or other deleterious mechanical behavior. This platform has the potential to be coupled with electrical sensors for simultaneous multisensor mapping of atrial fibrillation and other cardiac arrhythmias.
Pitolisant for Daytime Sleepiness in Patients with Obstructive Sleep Apnea Who Refuse Continuous Positive Airway Pressure Treatment. A Randomized Trial
Authors: Yves Dauvilliers, Johan Verbraecken, Markku Partinen, Jan Hedner, Tarja Saaresranta, Ognian Georgiev, Rumen Tiholov, Isabelle Lecomte, Renaud Tamisier, Patrick Lévy, Catherine Scart-Gres, Jeanne-Marie Lecomte, Jean-Charles Schwartz, Jean-Louis Pépin, Valerie Attali, Patrice Bourgin, Frederic Gagnadoux, Farhad Baharloo, Soren Berg, Olli Polo, Jan Anders Hedner, Yeksel Peker, Alexander Blau, Diego Garcia Borreguero, Francisco Javier Puertas Cuesta, Georgi Belev, Yavor Ivanov, Hristo Metev, Diana Petkova, Dejan Dokic, Merita Ismajli Marku, Biserka Jokovska Kaeva, Slavko Jankovic, Ivan Kopitovic, Miodrag Vukcevic
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Excessive daytime sleepiness is a common disabling symptom in obstructive sleep apnea syndrome.Objectives: To evaluate the efficacy and safety of pitolisant, a selective histamine H3 receptor antagonist with wake-promoting effects, for the treatment of daytime sleepiness in patients with moderate to severe obstructive sleep apnea refusing continuous positive airway pressure treatment.Methods: In an international, multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial, pitolisant was individually titrated at up to 20 mg/d over 12 weeks. The primary endpoint was the change in the Epworth Sleepiness Scale score. Key secondary endpoints were maintenance of wakefulness assessed on the basis of the Oxford Sleep Resistance test, safety, Clinical Global Impression of severity, patient’s global opinion, EuroQol quality-of-life questionnaire, and Pichot fatigue questionnaire.Measurements and Main Results: A total of 268 patients with obstructive sleep apnea (75% male; mean age, 52 yr; apnea–hypopnea index, 49/h; baseline sleepiness score, 15.7) were randomized (200 to pitolisant and 68 to placebo) and analyzed on an intention-to-treat basis. The Epworth Sleepiness Scale score was reduced more with pitolisant than with placebo (−2.8; 95% confidence interval, −4.0 to −1.5; P < 0.001). Wake maintenance tests were not improved. The Pichot fatigue score was reduced with pitolisant. The overall impact of pitolisant was confirmed by both physicians’ and patients’ questionnaires. Adverse event incidence, mainly headache, insomnia, nausea, and vertigo, was similar in the pitolisant and placebo groups (29.5% and 25.4%, respectively), with no cardiovascular or other significant safety concerns.Conclusions: Pitolisant significantly reduced self-reported daytime sleepiness and fatigue and improved patient-reported outcomes and physician disease severity assessment in sleepy patients with obstructive sleep apnea refusing or nonadherent to continuous positive airway pressure.Clinical trial registered with www.clinicaltrials.gov (NCT01072968) and EU Clinical Trials Register (EudraCT 2009-017251-94).
The Clinical Role of Peptide Vaccines for Castration-Resistant Prostate Cancer
Authors: T. Minami, T. Kimura, M. Nozawa, K. Yoshimura, T. Nakagawa, A. Yamada, K. Itoh, H. Fujimoto, S. Egawa, H. Uemura
Journal: Annals of Oncology (2012)
メタドキシンは、アルコール患者の脂肪肝の回復を加速する:ランダム化二重盲検プラセボ対照試験の結果
Authors: Caballeria J, Pares A, Bru C, Mercader J, Plaza A G, Caballeria L, Clemente G, Rodrigo L, Rodes J
Journal: Journal of Hepatology (1998)
Corrigendum to “Activation of biologically relevant levels of reactive oxygen species by Au/g-C3N4 hybrid nanozyme for bacteria killing and wound disinfection” [Biomaterials, 113(2017)145–157]
Authors: Zhenzhen Wang, Kai Dong, Zhen Liu, Yan Zhang, Zhaowei Chen, Hanjun Sun, Jinsong Ren, Xiaogang Qu
Journal: Biomaterials (2020)
Comparison of High-Dose Cyclophosphamide Plus G-CSF with G-CSF Alone for Peripheral Blood Stem Cell Mobilization in MM
Authors: J.E. Jang, S.Y. Hyun, D.Y. Hwang, S.H. Yoon, Y.D. Kim, S.J. Kim, J.S. Kim, J.-W. Cheong, Y.H. Min
Journal: Annals of Oncology (2012)
Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock
Authors: Tomoko Fujii, Nora Luethi, Paul J. Young, Daniel R. Frei, Glenn M. Eastwood, Craig J. French, Adam M. Deane, Yahya Shehabi, Ludhmila A. Hajjar, Gisele Oliveira, Andrew A. Udy, Neil Orford, Samantha J. Edney, Anna L. Hunt, Harriet L. Judd, Laurent Bitker, Luca Cioccari, Thummaporn Naorungroj, Fumitaka Yanase, Samantha Bates, Forbes McGain, Elizabeth P. Hudson, Wisam Al-Bassam, Dhiraj Bhatia Dwivedi, Chloe Peppin, Phoebe McCracken, Judit Orosz, Michael Bailey, Rinaldo Bellomo
Journal: JAMA (2020)

It is unclear whether vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock. To determine whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock. Multicenter, open-label, randomized clinical trial conducted in 10 intensive care units in Australia, New Zealand, and Brazil that recruited 216 patients fulfilling the Sepsis-3 definition of septic shock. The first patient was enrolled on May 8, 2018, and the last on July 9, 2019. The final date of follow-up was October 6, 2019. Patients were randomized to the intervention group (n = 109), consisting of intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours), or to the control group (n = 107), consisting of intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days. The primary trial outcome was duration of time alive and free of vasopressor administration up to day 7. Ten secondary outcomes were prespecified, including 90-day mortality. Among 216 patients who were randomized, 211 provided consent and completed the primary outcome measurement (mean age, 61.7 years [SD, 15.0]; 133 men [63%]). Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], 76.3-145.4 hours) in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was -0.6 hours (95% CI, -8.3 to 7.2 hours; P = .83). Of 10 prespecified secondary outcomes, 9 showed no statistically significant difference. Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69-2.00). No serious adverse events were reported. In patients with septic shock, treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days. The finding suggests that treatment with intravenous vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone. ClinicalTrials.gov Identifier: NCT03333278.
P-0051 Prognostic Factors Correlated to Poor Outcome Among Patients with Potentially Curable Gastric Cancer Treated with Perioperative Chemotherapy
Authors: Cinta Hierro Carbó, Martín Francisco Javier Pérez, Maria José Paules, Gloria Hormigo, Farran Leandre, Humberto Aranda, Glòria Creus, Richard Mast, Joan Berenguer Gornals, Mariona Calvo, Maica Galán
Journal: Annals of Oncology (2012)
Periodic Measurement of N-Telopeptides of Type I Collogen in Serum (SNTX) for Early Diagnosis of Bone Metastasis in Patients with Lung Cancer
Authors: H. Daga, H. Okada, K. Taira, S. Tokunaga, K. Takeda, N. Miyamoto, M. Hattori, M. Tamiya, M. Kobayashi, N. Okamoto, S. Sasada, H. Suzuki, N. Morishita, Y. Matsuura, T. Hirashima
Journal: Annals of Oncology (2012)
Heat Shock Protein 90 Inhibition Downregulates C-Kit Expression in Gist Cells Through Diminishing Transcription and Enhancing Protein Degradation via both Autophagy and Proteasome Pathways
Authors: Y. Hsueh, C. Yen, N. Shih, N. Chiang, C. Li, L. Chen
Journal: Annals of Oncology (2012)
m6A demethylase ALKBH5 inhibits pancreatic cancer tumorigenesis by decreasing WIF-1 RNA methylation and mediating Wnt signaling
Authors: Bo Tang, Yihua Yang, Min Kang, Yunshan Wang, Yan Wang, Yin Bi, Songqing He, Fumio Shimamoto
Journal: Molecular Cancer (2020)

Abstract Background Pancreatic cancer is one of the most lethal types of cancer with extremely poor diagnosis and prognosis, and chemo-resistance remains a major challenge. The dynamic and reversible N 6 -methyladenosine (m 6 A) RNA modification has emerged as a new layer of epigenetic gene regulation. Methods qRT-PCR and IHC were applied to examine ALKBH5 levels in normal and pancreatic cancer tissues. Cancer cell proliferation and chemo-resistance were evaluated by clonogenic formation, chemosensitivity detection, and Western blotting assays. m 6 A-seq was performed to identify target genes. We evaluated the inhibitory effect of ALKBH5 in both in vivo and in vitro models. Results Here, we show that m 6 A demethylase ALKBH5 is downregulated in gemcitabine-treated patient-derived xenograft (PDX) model and its overexpression sensitized pancreatic ductal adenocarcinoma (PDAC) cells to chemotherapy. Decreased ALKBH5 levels predicts poor clinical outcome in PDAC and multiple other cancers. Furthermore, silencing ALKBH5 remarkably increases PDAC cell proliferation, migration, and invasion both in vitro and in vivo, whereas its overexpression causes the opposite effects. Global m 6 A profile revealed altered expression of certain ALKBH5 target genes, including Wnt inhibitory factor 1 ( WIF-1 ), which is correlated with WIF-1 transactivation and mediation of the Wnt pathway. Conclusions Our work uncovers the tumor suppressive and chemo-sensitizing function for ALKBH5, which provides insight into critical roles of m 6 A methylation in PDAC.
P-0197 Common VEGF Gene Polymorphisms are Not Associated With Relapse-Free Survival in Colorectal Cancer Patients
Authors: Guenter Hofmann, Tanja Langsenlehner, Florentine Moazedi-Fuerst, Armin Gerger, Sonja Kielhauser, Gudrun Absenger, Joanna Szkandera, Hellmut Samonigg, Peter Krippl, Wilfried Renner
Journal: Annals of Oncology (2012)
Abstract 407: Utility of Abnormal Head Computed Tomography in Predicting Outcome in Out of Hospital Cardiac Arrest Victims Resuscitated and Subsequently Placed on Targeted Temperature Management
Authors: Michael Bernett, Robert A Swor
Journal: Circulation (2019)

Introduction: Head computed tomography (HCT) is often performed to assess for hypoxic-ischemic brain injury in resuscitated out of hospital cardiac arrest (OHCA) patients. Our primary objective was to assess whether cerebral edema (CE) on early HCT is associated with poor survival and neurologic outcome post OHCA. Methods: We included subjects from a prospectively collected cardiac arrest database of OHCA adult patients who received targeted temperature management (TTM) at two academic suburban hospitals from 2009-Sept-2018. Cases were included if a HCT was performed in the emergency department (ED). Patient demographics and cardiac arrest variables were collected. HCT results were abstracted by study authors from radiology reports. HCT findings were categorized as no acute disease, evidence of CE, or excluded (bleed, tumor, stroke). Outcomes were survival to discharge or cerebral performance scores (CPC) at discharge of three or four (poor neurologic outcome). Descriptive statistics, univariate, multivariate, survival, and interrater reliability analysis were performed. Results: During the study period, there were 425 OHCA, 277 cases had ED HCTs performed; 254 cases were included in the final survival analysis. Patients were predominately male, 189 (65.0%), average age 60.9 years, average BMI of 30.5. Of all cases, 44 (15.9%) showed CE on CT. Univariate analysis demonstrated that CE was associated with 9.2-fold greater odds of poor outcome (OR: 9.23; 95% CI 1.73, 49.2), and 9.1-fold greater odds of death (OR: 9.09: 95% CI 2.4 33.9). In adjusted analysis, CE was associated with 14.9-fold greater odds of poor CPC outcome (AOR: 14.9, 95% CI, 2.49, 88.4), and 13.7-fold greater odds of death (AOR: 13.7, 95% CI, 3.26, 57.4). Adjusted survival analysis demonstrated that patients with CE on HCT had 3.6-fold greater hazard of death than those without CE (HR: 3.56: 95% CI 2.34, 5.41). Interrater reliability demonstrated excellent agreement between reviewers for CE on HCT (κ = 0.86). Conclusion: The results identify that abnormal HCTs early in the post-arrest period in OHCA patients are associated with poor rates of survival and neurologic outcome. Prospective work is needed to confirm whether selection bias or other variables confound this association.