tbuckley/cabot-search huggingface dataset:
Molecular characteristics and metastasis predictor genes of triple-negative breast cancer.
Authors: Wen-Hung Kuo, Yao-Yin Chang, Ming-Feng Hou, Eric Y Chuang, King-Jen Chang
Journal: Journal of Clinical Oncology (2012)

1043 Background: Triple-negative breast cancer(TNBC) is a subtype of breast cancer with aggressive tumor behavior and distinct disease etiology. Due to the lack of an effective targeted medicine, treatment options for triple-negative breast cancer are few and recurrence rates are high. Although various multi-gene prognostic markers have been proposed for the prediction of breast cancer outcome, most of them were proven clinically useful only for estrogen receptor-positive breast cancers. Reliable identification of triple-negative patients with a favorable prognosis is not yet possible. Methods: Clinicopathological information and microarray data from 157 invasive breast carcinomas were collected at National Taiwan University Hospital from 1995 to 2008. Gene expression data of 51 triple-negative and 106 luminal breast cancers were generated with oligonucleotide microarrays. A prognostic 45-gene signature for triple-negative breast cancer was identified using Student’s t test and receiver operating characteristic analysis. Results: Hierarchical clustering analysis revealed that the majority (94%) of triple-negative breast cancers were tightly clustered together carrying strong basal-like characteristics. A novel 45-gene signature giving 98% predictive accuracy in distant metastasis recurrence was identified in our triple-negative patient cohort. External validation of the prognostic signature in an independent microarray dataset of 59 early-stage triple-negative patients also obtained statistical significance (hazard ratio 2.29, 95% CI 1.04-5.06, Cox P = 0.04), outperforming five other published breast cancer prognostic signatures. The prognostic signature was statistically predictive with the node-negative triple-negative patients in the validation cohort. Conclusions: The 45-gene prognostic signature identified in this study revealed that TGF-β signaling in immune/inflammatory regulation may be critically involved in distant metastatic invasion of TNBC. The 45-gene signature, if further validated, may be a clinically useful tool in risk assessment of metastasis recurrence for early-stage triple-negative patients.
DOES POST PCI FFR CARRY THE SAME PROGNOSTIC WEIGHT AS NON-ISCHEMIC FFR IN DEFERRED LESIONS?
Authors: Mohammed Eid Madmani, Amjad Abualsuod, Mohan Edupuganti, Shiv Kumar Agarwal, Srikanth Kasula, Naga Venkata Pothineni, Ahmed Almomani, Jason Payne, Barry Uretsky, Abdul Hakeem
Journal: Journal of the American College of Cardiology (2017)
The risk of early occurrence and recurrence of hepatocellular carcinoma in hepatitis C infected patients treated with direct acting antivirals with and without pegylated interferon: a Belgian experience
Authors: R. Bielen, C. Moreno, H. Van Vlierberghe, S. Bourgeois, J.-P. Mulkay, S. Francque, W. Verlinden, C. Brixko, J. Decaestecker, C. De Galocsy, F. Janssens, M. Cool, C. Van Steenkiste, F. D’heygere, K. Wuyckens, F. Nevens, G. Robaeys
Journal: Journal of Hepatology (2017)
CLOPIDOGREL IS NOT COMMONLY USED BUT ASSOCIATED WITH LESS RE-HOSPITALIZATION IN PATIENTS WITH PERIOPERATIVE MYOCARDIAL INFARCTION FOLLOWING CABG SURGERY
Authors: Alice Wang, Angie Wu, Daniel Wojdyla, Renato Lopes, L. Kristin Newby, Mark Newman, Peter K. Smith, John Alexander
Journal: Journal of the American College of Cardiology (2017)
CLINICAL CHARACTERISTICS AND CHANGES OF VALVULOARTERIAL IMPEDENCE SEVERITY IN PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT FOR SEVERE AORTIC STENOSIS
Authors: Aarti A. Patel, Vishal Parikh, Allen Brown, Joseph Coffman, Fadi Matar, Christiano Caldeira, Robert Hooker, J. Thompson Sullebarger, Kevin Kip, Arthur Labovitz, Allan Chen
Journal: Journal of the American College of Cardiology (2017)
Utility of endometrial sampling in the detection of uterine sarcomas
Authors: N. Bansal, T. J. Herzog, C. J. Cohen, J. D. Wright
Journal: Journal of Clinical Oncology (2007)

20527 Objective: Uterine sarcomas are aggressive tumors that are often not recognized prior to surgical exploration. The goal of this study was to determine the utility of endometrial sampling in the detection of uterine sarcomas and to examine factors associated with diagnostic inaccuracy. Methods: All uterine tumors identified in hysterectomy specimens from 1990 to 2006 were accessioned. Study participation required a preoperative endometrial sampling (biopsy or curettage) that was reviewed at our center. Pathologic data and follow-up was documented through review of hospital records. Statistical analysis was performed using Fisher's exact test. Results: A total of 938 patients were identified. A preoperative biopsy was available for review in 730 (78%) subjects. Uterine sarcomas were noted in 142 patients; 72 (51%) underwent preoperative sampling. Overall, endometrial sampling correctly identified an invasive tumor in 88% (642/730). The correct histologic diagnosis was rendered in 80% (585/730). Among women with sarcomas, the preoperative sampling suggested a tumor in 86% (62/72) and predicted the correct histologic diagnosis in 64% (46/72). Among patients with epithelial carcinomas, biopsy suggested a tumor in 88% (569/644) and made the correct histologic diagnosis in 84% (539/644). Preoperative endometrial sampling was less accurate in patients with uterine sarcomas than in women with epithelial carcinomas (missed diagnosis 36% vs. 16%) (p &lt; 0.0001). Subgroup analysis indicated that the histologic diagnosis was incorrect in 39% of the sarcoma patients who underwent office biopsy compared to 34% of those who underwent endometrial curettage (p=0.8). Patients with carcinosarcomas were more likely to undergo preoperative sampling than those with leiomyosarcomas (77% vs. 33%) (p=0.001). Conclusions: Endometrial sampling has a significantly lower predictive value in the diagnosis of uterine sarcomas. There is no difference in accuracy between office endometrial biopsy and uterine curettage. Novel diagnostic techniques are needed to accurately identify uterine sarcomas preoperatively. No significant financial relationships to disclose.
Prognostic factors of response to adjuvant chemotherapy after curative resection for pancreatic ductal adenocarcinoma: Prognostic impact of CDA, predictive value of DPD for 5FU efficiency, and hENT1 for gemcitabine.
Authors: Xavier Edouard Truchet, Claire Mallaret, Véronique Secq, Julien Mancini, Yves patrice le Treut, Vincent Moutardier, Mehdi Ouaïssi, Marion Rubis, Emilie Nouguered, Jean Delgrande, marie-Noëlle Lavaut, Joseph Ciccolini, Mohamed Gasmi, Stéphane Garcia, Jean Francois Seitz, Laetitia Dahan
Journal: Journal of Clinical Oncology (2014)

e15191 Background: Since 2005, adjuvant chemotherapy with gemcitabine (Gem) or 5fluorouracil (5FU) plus folinic acid for 6 months is a standard in resected pancreatic cancer. Predictive factors of efficiency of these 2 schemes seems necessary to offer patients a treatment card. This retrospective study evaluated the prognostic value of 7 histological markers (DPD, TS, CDA, hENT1, hCNT3, S100A2, and SMAD 4), and their impact on the efficacy chemotherapy with Gem or 5FU. Methods: From 230 pancreatic resections for cancer, we retrospectively included 193 patients with pancreatic surgery for pancreatic adenocarcinoma (PAC) between March 2005 and December 2012 in three hospitals in Marseille. A TMA (Tissue Micro Array) was constructed using tissue core samples from these tumors. Of these, 63 patients were excluded from the analysis: 9 early postoperative deaths, 7 metastatic disease or R2 resection, 6 received neo-adjuvant treatment, 14 lost of follow up, 27 not included in the TMA. Finally, 123 patients were available: 108 received postoperative chemotherapy (69 GEM, 32 LV5FU2, 7 others), 13 didn't receive adjuvant treatment and 2 was unknown. 7 immunohistochemical markers were performed on the TMA: SMAD 4, TS, hCNT3, DPD, CDA, hENT1, S100A2. Results: OS was increased in patients with no CDA tumoral expression versus low or high (38.6 months vs 20.7 months p = 0.03). This difference remained significant in multivariate analysis (p = 0.02). Intratumoral overexpression of DPD is a pejorative predictive factor of OS and RFS in patients treated with 5FU: Respectively 25.7 months for none or low expression vs 10.4 months for high expression (p = 0.04), and 12.3 months vs 4.9 months, (p = 0.04). Intratumoral high expression of hENT1 is a predictive factor of better RFS in patients receiving Gem (14.9 months vs 11.5 months, p= 0.045). Conclusions: Loss of expression of intratumoral CDA is prognostic of better survival in patients undergoing curative PAC. The low expression of DPD is predictive of better OS and RFS in patients treated with 5FU. High expression of hENT1 is predictive of better RFS in patients treated with Gem.
Clinical activity and cardiac tolerability of metronomic non-pegylated liposomal doxorubicin in heavily pre-treated patients with metastatic breast cancer: A single institucion experience.
Authors: Katerin Ingrid Rojas, Luis Manso, Juan Manuel Sepúlveda, Cesar Mendiola, Tomas Pascual, Eva Ciruelos, Luis Paz-Ares
Journal: Journal of Clinical Oncology (2015)

e11570 Background: Due to its low cardiac toxicity, non-pegylated liposomal doxorubicin (NPLD) may represent an attractive therapeutic option as salvage therapy for patients (pts) with metastatic breast cancer (BC) who have alredy received antracycline-based chemotherapy (CT).The aim of this study was to review clinical activity and cardiac tolerability. Methods: We performed a systematic retrospective analysis of all 112 pts with heavily pretreated metastatic BC treated with the Metronomic-Cooper-type regimen consisting of weekly NPLD (30mg IV) plus 5-Fluorouracil (5-FU)(500mg IV) plus vincristine (0.25mg IV) and daily oral cyclophosphamide (50mg) plus prednisone (20mg) until disease progression or unacceptable toxicity and prophylaxis with trimethoprim/sulfamethoxazole 160/800mg three times a week for pneumocystis jiroveccii, were reviewed at our Institution between December 2000 to July 2014. Results: The average previous lines of CT was 3 (range 1-14). Twenty-seven pts (24.10%) achieved a partial response and 42 (37.50%) had stable disease, with a disease control rate of 62%; 41 pts (36.60%) had progressive disease. The median progression-free survival and overall survival were 4,66 and 10,5 months respectively. The most common grade 2-3 hematologic adverse events was neutropenia, which was observed in 26 pts (23.21%). Febrile neutropenia was observed in 11 pts (9.82%). The most common non-hematologic adverse events were asthenia and mucositis which were observed in 50 pts (44.64%) and 20 pts (17.85%) respectively. Two pts (1.78%) experienced a decline of the left ventricular ejection fraction. Conclusions: Weekly NPLD represents a safe and effective therapy and may be considered a therapeutic option for heavily pre-treated pts with BC and cardiac risk factors.
Does aggressive primary debulking surgery influence survival in ovarian cancer?
Authors: Yakir Segev, Barry Rosen, Joan Murphy, Stephane Laframboise, Jason Esli Dodge, Sarah E Ferguson, Marcus Bernardini, Brendan Charles, Ping Sun, Steven Narod
Journal: Journal of Clinical Oncology (2013)

5561 Background: Evidence comparing outcomes in patients receiving primary debulking surgery (PDS) to those receiving neoadjuvant chemotherapy (NACT) for advanced stage ovarian carcinoma is conflicting. We conducted a retrospective survival analysis of all patients with stage IIIC and IV serous ovarian cancer treated at our institute by either PDS or NACT. Methods: Data was extracted from patient synoptic OR reports and medical records between January 2003 and December 2011. Survival comparisons between patients receiving NACT and PDS were made according to aggressiveness of surgery and residual disease following surgery. Aggressive surgery was defined by one of the following procedures; pelvic peritonectomy, any bowel resection, diaphragm resection, diaphragm peritonectomy and splenectomy. Results: Out of 342 patients, 143 (41%) had NACT and 199 (59%) had PDS. Patients undergoing PDS had a median survival (MS) of 58 months compared to 34 months for NACT. Patients undergoing PDS with &gt; 10mm and &lt;10mm residual disease, had a MS of 33 and 55 months, respectively; whereas those with microscopic disease have not yet reached their MS. In the NACT group, MS for &lt; and &gt; 10 mm residual disease was 30 months for both, compared with 39 months for those with microscopic disease. Within the PDS group, those undergoing limited surgery had a MS of 48 months whereas MS has not been reached for those undergoing aggressive surgery. Over 60% of patients undergoing PDS with microscopic residual were alive at 7 years. In the NACT group, there was no difference in survival according to extent of surgery. Conclusions: Patients withPDS, whether debulked to &lt; 10mm or to microscopic disease have a significant and lengthy survival advantage over patients receiving NACT.
Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome
Authors: Roy G Brower, Michael A Matthay, Alan Morris, David Schoenfeld, B Taylor Thompson, Arthur Wheeler
Journal: New England Journal of Medicine (2000)

Original Article from The New England Journal of Medicine — Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome
포스터전시 : 국내 만성 C형 간염 환자에서 페그인터페론과 리바비린 병합요법의 임상 성적 (초)
Authors: 이동석, 권영오, 박수영, 조창민, 탁원영, 허정, 조몽, 윤기태, 우현영
Journal: Clinical and Molecular Hepatology (2010)
Modulation of plasma cytokines and its association with clinical response to treatment with the JAK2-selective inhibitor SAR302503 in myelofibrosis (MF).
Authors: Moshe Talpaz, Catriona H. M. Jamieson, Nashat Y. Gabrail, Claudia Lebedinsky, Feng Liu, Hui Cao, Ayalew Tefferi, Animesh Dev Pardanani
Journal: Journal of Clinical Oncology (2013)

7110 Background: Abnormal cytokine expression may represent an inflammatory response that contributes to the clinical phenotype of MF. Some constitutional symptoms (eg. fever, fatigue, pruritus, cachexia) are thought to be caused by elevated cytokines. In phase I/II studies, SAR302503 reduced splenomegaly and constitutional symptoms in patients with MF. Here, we report the effects of SAR302503 on the expression of 97 cytokines in MF patients enrolled in a Phase II study (NCT01420770) and the relationship to clinical response (spleen size), pharmacokinetic (PK) exposure, and body weight changes. Methods: Thirty-one patients were randomized to receive 300, 400, or 500 mg of SAR302503 orally, once daily, continuously in 4-week cycles. Plasma cytokines were measured at baseline and at the end of 4, 8, and 12 weeks of treatment using a microsphere-based immuno-multiplex assay (Rules Based Medicine). Results: Complete sample sets were available for 29/31 patients. A total of 28 cytokines predominantly involved in immune/inflammation pathways were regulated ≥1.5-fold (ANOVA P&lt;0.05) and of these, 19 were regulated at all time points, indicating rapid and sustained modulation by JAK2 inhibition. At 4 weeks, 16 cytokines were down-regulated, including TNFα, IL-1RA, and IL-18, and 6 were up-regulated, including leptin, EPO, and adiponectin. Hierarchical clustering of the 22 regulated cytokines enriched patients into spleen responder (≥35% reduction in spleen volume by MRI) and non-responder groups, suggesting a link between cytokine modulation and clinical response. Moderate correlations (P&lt;0.05) with spleen volume reduction at the end of week 12 were seen for a subset of regulated cytokines, including adiponectin and TNFα. Levels of the majority of the regulated cytokines tended to correlate with steady state PK exposure at week 4. A positive association with weight changes at week 24 were observed for leptin and adiponectin at week 4 (P&lt;0.05). Conclusions: This analysis shows that SAR302503 treatment modulated the expression of circulating cytokines in MF patients in association with changes in clinical activity, PK exposure, and symptom improvement (weight gain). Clinical trial information: NCT01420770.
IMPACT OF SALINE INDUCED PD/PA RATIO FOR PREDICTING FUNCTIONAL SIGNIFICANCE OF INTERMEDIATE CORONARY ARTERY STENOSIS ASSESED BY FRACTIONAL FLOW RESERVE
Authors: Yoshiharu Fujimori, Satoshi Hashimoto, Kenichiro Ebisuda, Kazuto Kurihara, Yasushi Yamanaka, Tomoko Baba, Tomoyuki Seki, Shigeru Nishiyama, Shiho Mizutani, Kyohei Yamazaki, Tadamasa Wakabayashi, Taku Imai
Journal: Journal of the American College of Cardiology (2017)
Preventing insulin dependent diabetes mellitus: the environmental challenge. Diabetes Epidemiology Research International.
Authors: Ronald Laporte, Janice Dorman, Trevor Orchard, Dorothy Becker, Allan Drash, Jaakko Tuomilehto, Paul Zimmet, Moshe Karp
Journal: BMJ (1987)

The epidemiology of insulin dependent diabetes mellitus was evaluated to determine the degree to which the disease results from environmental agents and therefore might be prevented. The results of research indicate that insulin dependent diabetes can be produced in animal models by environmental factors, there are major geographical variations in diabetes, certain populations have shown rapid changes in incidence over time, migrants appear to take on the risk of diabetes in their new country, and certain viruses and chemicals cause insulin dependent diabetes in humans. The results of genetic and epidemiological studies also show that at least 60% of insulin dependent diabetes world wide, and perhaps over 95%, is environmentally determined and thus potentially avoidable. It is concluded that the primary worldwide determinants of diabetes are environmental not immunogenetic and that identifying and altering the diabetogenic environmental factor(s) are likely to be more effective and less risky in preventing insulin dependent diabetes than current immunogenetic approaches.
Comparison of BRCA1/2-positive and -negative women diagnosed with metachronous breast and ovarian cancers.
Authors: Amanda C. Brandt, Nisreen Elsayegh, Heather Lin, Angelica M. Gutierrez-Barrera, Karen H. Lu, Banu Arun
Journal: Journal of Clinical Oncology (2012)

1546 Background: After a primary breast cancer (BC) or ovarian cancer (OC) diagnosis, women have a risk to develop a second primary cancer, significantly more so in women with a BRCA gene mutation. The objective was to evaluate characteristics of BRCA positive and negative women diagnosed with metachronous BC and OC. Methods: Women with metachronous BC and OC were identified at the University of Texas MD Anderson Cancer Center. BRCA test results, age at diagnosis of both BC and OC, first degree relatives (FDR) with BC and/or OC, total relatives affected, and histopathologic tumor features were obtained from a prospectively maintained research database. Univariate and logistical regression analyses were performed. Results: A total of 64 women with metachronous primary cancers underwent BRCA genetic testing. Of the 45 BRCA positive women, 36 (80%) were diagnosed with BC (mean 40 years) prior to OC and 9 (20%) were diagnosed with OC first (mean 47 years). Of the 19 BRCA negative women, 10 (53%) were diagnosed with BC first (mean 63 years), and 9 (47%) diagnosed with OC first (mean 48 years). Women diagnosed with BC first were more likely to be BRCA positive than women diagnosed with OC first (p=0.03). Patients with a FDR with BC were more likely BRCA positive than women without family history (p=0.0062). Patients with PR negative BR (p=0.0199) or triple negative (TN) BC (p=0.0139) were more likely to test BRCA positive. High grade ovarian carcinomas approached significance (p=0.053) in BRCA positive when compared to BRCA negative cohort. Ethnicity, total number of affected relatives with BC or OC, ER status, Her2 status, and nuclear grade were not statistically significant between the two groups. Conclusions: Women with OC preceding their BC with lack of family history of BC and OC are significantly less likely to test BRCA positive. BC is often the sentinel cancer in women with a BRCA mutation compared to BRCA negative women with metachronous BC and OC. This should be considered during the risk assessment to more accurately estimate the chance of identifying a BRCA mutation in women with metachronous BC and OC.
HEALTH-ECONOMICS OF MEASURING HIGH-SENSITIVE CARDIAC TROPONIN AT DIFFERENT CUT-OFFS IN NON-ST SEGMENT ELEVATION MYOCARDIAL INFARCTION PATIENTS WITHIN 6 HOURS FROM EMERGENCY ROOM PRESENTATION
Authors: Deepak Kumar Sahu, Giacomo Basadonna, Michal Raciborski
Journal: Journal of the American College of Cardiology (2017)
OPTOGENETIC APPROACH MODULATES CARDIAC SYMPATHETIC GANGLION TO PROTECT AGAINST ISCHEMIA RELATED VENTRICULAR ARRHYTHMIAS
Authors: Lilei Yu, Liping Zhou, Bing Huang, Zhuo Wang, Songyun Wang, Menglong Wang, Xuefei Li, Guannan Meng, Shenxu Yuan, Yuhong Wang, Xiaoya Zhou, Hong Jiang
Journal: Journal of the American College of Cardiology (2017)
Phase I/II study of dianhydrogalactitol in patients with recurrent malignant glioma or progressive secondary brain tumor.
Authors: James D. Peyton, Howard A. Burris, Jeffrey A. Bacha, Dennis Brown, William J. Garner, Richard Stephen Schwartz, Kent C. Shih
Journal: Journal of Clinical Oncology (2013)

2093 Background: Recurrent glial tumors of the brain continue to be one of the most challenging malignancies to treat, and median survival for patients with recurrent disease is approximately 6 months for glioblastoma multiforme (GBM). The front-line therapy for GBM - temozolomide (TMZ) - is subject to resistance by DNA repair protein O 6 -methylguanine-DNA methyltransferase (MGMT), leading to poor prognoses for patients with recurrent GBM. Dianhydrogalactitol (VAL-083)is a first-in-class bi-functional N 7 DNA alkylating agent shown to cross the blood-brain barrier, accumulate in brain tissue, and have activity against GBM. Studies suggest that VAL-083 overcomes MGMT-driven drug resistance in vitro and targets cancer stem cells. The purpose of this study is to determine the maximal tolerated dose (MTD) of VAL-083 in patients with recurrent GBM or progressive secondary brain tumor, and explore the safety, pharmacokinetics and tumor responses to treatment. Methods: Open-label phase I/II dose-escalation study of VAL-083 in patients with histologically confirmed primary WHO grade 4 malignant GBM, now recurrent, previously treated for GBM with surgery and/or radiation, if appropriate, and have failed both bevacizumab and temozolomide; or progressive secondary brain tumor, has failed standard brain radiotherapy, and has brain tumor progression after at least one line of systemic therapy. The study uses a 3 + 3 dose escalation design, until reaching the MTD or maximum specified dose. Patients receive IV VAL-083 on days 1, 2, and 3 of each 21-day treatment cycle. In phase II, additional patients are treated at the MTD (or selected optimum dose) to measure tumor responses. Results: Cohort 1 (3 patients) and cohort 2 (4 patients) were completed without any DLT’s. Adverse events (AEs) have all been grade 1/2, with only 1 grade 3 AE, unrelated to treatment. Cohort 3 currently has 4 patient enrolled, without reaching the MTD. 1/7 (14.3%) patients in cohorts 1and 2 has prolonged stable disease (15+ cycles) on VAL-083 treatment. Conclusions: VAL-083 up to the 2nd dose level was well tolerated without any safety signals. Dose escalation is continuing. Clinical trial information: NCT01478178.
Indatuximab Ravtansine (BT062) in Combination with Low-Dose Dexamethasone and Lenalidomide or Pomalidomide: Clinical Activity in Patients with Relapsed / Refractory Multiple Myeloma
Authors: Kevin R. Kelly, David S. Siegel, Asher A. Chanan-Khan, George Somlo, Leonard T. Heffner, Sundar Jagannath, Todd Zimmerman, Nikhil C Munshi, Sumit Madan, Ann Mohrbacher, Sagar Lonial, Farima Barmaki-Rad, Markus Rühle, Eva Herrmann, Andrea Wartenberg-Demand, Thomas Haeder, Kenneth C. Anderson
Journal: Blood (2016)