tbuckley/cabot-search huggingface dataset:
Angiotensin II receptor blockade effect on sensitivity to salvage radiotherapy after prostatectomy.
Authors: Hiroji Uemura, Yumiko Yokomizo, Yusuke Itoh, Kouji Izumi, Narihiko Hayashi, Yoshinobu Kubota
Journal: Journal of Clinical Oncology (2014)

e16078 Background: Our previous report indicated that angiotensin II receptor blockers (ARB) have the potential to decrease or stabilize PSA level of patients with CRPC and inhibit the occurrence of symptoms. Furthermore, we confirmed that ARB can slow down the PSA increasing after prostatectomy. In this study, we examined the influence of ARB on the radiosensitivity in patients treated with salvage radiation (SRT) after PSA failure of the prostatectomy. Methods: After IRB approval was obtained, data from 457 patients undergoing RP at Yokohama City University Hospital and Center Hospital from January 2000 to April 2013 were entered into our database. Biochemical failure (BCF) was defined as a single PSA level of >0.2 ng/mL. SRT was offered to men with BCF after prostatectomy. At BCF of PSA values, men with hypertension received olmesartan (Dai-ichi Sankyo Co., Tokyo), an ARB, at 10-20 mg once daily till their PSA values were over 1.0 ng/mL. Results: Among 131 patients with BCF, 44 (33.6%) received SRT for BCF or persistent PSA levels during a median follow-up of 87.2 months after prostatectomy and 53.4 months after SRT. Median PSA level before SRT was 1.12 ng/mL. Good responders with <0.2 ng/mL were 30 patients (68.2%) and median non-BCF rate of all patients was 48 months after SRT. Gleason score (GS) was an independent predictor of the BCF interval after SRT. In brief, there was a significant difference of non-BCF (P=0.047) between GS≥8 and GS≤7. Men administered ARB (n=18) were more likely to respond favorably to SRT compared with non-ARB group (n=26). Their median non-BCF intervals were NR of ARB group and 33.5 months of non-ARB group, respectively (P=0.058). Limitations of this study are the retrospective design and limited follow-up duration. Conclusions: Although in our study the efficacy of SRT was similar outcome of previous reports, it should be noted that ARB administration showed the radiosensitivity after BCF of prostatectomy. Our previous investigations indicate the anti-tumor effect of prostate cancer by ARB, and additionally a new concept that ARB has a possible potential of enhancing radiosensitivity for prostate cancer occurs from these data.
SEER-analysis of outcomes for primary small cell carcinoma of the breast.
Authors: Felicia Hare, Jashmin Kirankumar Patel, Moon Jung Fenton, Michael Gary Martin
Journal: Journal of Clinical Oncology (2014)

e12040 Background: Primary small cell carcinoma of the breast (SCCB) is rare and prognosis and outcomes are largely undefined. Methods: Using case listing session of SEER 18 (1973-2010) we examined outcomes for patients (pts) with SCCB. Analyses were conducted with SEER*Stat 8.1.2, Microsoft Excel 2007 and GraphPad Prism 6. Comparisons were made using the chi-squared test and log rank test (Mantel-Cox); all p-values were 2-sided. Results: 199 pts with primary SCCB of the breast with staging were identified; median age was 65 (range 28-97); 98% were female. 84 (42%) had localized disease (dz), 77 (39%) had regional dz and 38 (19%) had distant dz. 95% of pts with localized dz and 88% of pts with regional dz had breast surgery. Median overall survival (OS) varied by stage (150 months [m] v 56m v 7m, p<0.001) and radiation did not impact OS for pts with either localized (202m v 147m, p=0.477) or regional (52m v 75m, p=0.650) dz. For comparison 81,933 cases of small cell lung cancer (SCLC) were identified; 8% localized, 29%regional and 63% distant disease. Outcomes were superior for pts with SCCB with localized (150m v 16m, p<0.001) and regional dz (56m v 13m, p<0.001) but not distant dz (7m v 7m, p=0.043). Conclusions: SCCB presents at an earlier stage than and has a more favorable prognosis by stage for localized and regional dz than SCLC. Radiation does not appear to benefit patients with localized or regional SCCB, the majority of which had surgery.
Large DNA Methylation Canyons Anchor Chromatin Loops Maintaining Hematopoietic Stem Cell Identity
Authors: Mira Jeong, Xiangfan Huang, Xiaotian Zhang, Jianzhong Su, Muhammad S Shamim, Ivan D Bochkov, Jaime M. Reyes, Haiyoung Jung, Emily Beth Heikamp, Aviva P Aiden, Wei Li, Erez Lieberman Aiden, Margaret A. Goodell
Journal: Blood (2018)
Membrane-Anchored Serine Proteases and Protease-Activated Receptor-2–Mediated Signaling: Co-Conspirators in Cancer Progression
Authors: Nisha R. Pawar, Marguerite S. Buzza, Toni M. Antalis
Journal: Cancer Research (2019)

Pericellular proteolysis provides a significant advantage to developing tumors through the ability to remodel the extracellular matrix, promote cell invasion and migration, and facilitate angiogenesis. Recent advances demonstrate that pericellular proteases can also communicate directly to cells by activation of a unique group of transmembrane G-protein-coupled receptors (GPCR) known as protease-activated receptors (PAR). In this review, we discuss the specific roles of one of four mammalian PARs, namely PAR-2, which is overexpressed in advanced stage tumors and is activated by trypsin-like serine proteases that are highly expressed or otherwise dysregulated in many cancers. We highlight recent insights into the ability of different protease agonists to bias PAR-2 signaling and the newly emerging evidence for an interplay between PAR-2 and membrane-anchored serine proteases, which may co-conspire to promote tumor progression and metastasis. Interfering with these pathways might provide unique opportunities for the development of new mechanism-based strategies for the treatment of advanced and metastatic cancers.
Abstract 18337: The Role of NANOG in Regulating Fetal Liver Kinase-1 (FLK1) Expression in Angiogenesis
Authors: Erin Kohler, Asrar B Malik, Kishore K Wary
Journal: Circulation (2010)

Rationale: Fetal Liver Kinase-1 (FLK1) has a recognized role in endothelial cell (EC) formation, migration, and angiogenesis; although, its mechanism of action is not well known. Hypothesis: NANOG ...
Multiple Myeloma in Hispanics Is Associated with Better Survival Than Non-Hispanic African Americans and Whites: Analysis from a Large Single Center Minority Rich Cohort
Authors: Gurbakhash Kaur, Mateo Mejia Saldarriaga, Ana Acuna-Villaorduna, Mohammad Kazemi, Sakshi Jasra, Nishi Shah, Ioannis Mantzaris, Aditi Shastri, Olga Derman, Noah Kornblum, Ira Braunschweig, Amit Verma, Murali Janakiram
Journal: Blood (2018)
Relationships between occurrence of chills and clinical outcome during NGR-hTNF therapy.
Authors: Alessandra Bulotta, Vanesa Gregorc, Gilda Rossoni, Maria Grazia Viganò, Gabriele Todisco, Antonio Lambiase, Claudio Bordignon
Journal: Journal of Clinical Oncology (2014)

2538 Background: NGR-hTNF, a selective antivascular agent, quickly and transiently modulates the release of systemic cytokines/chemokines. Intravenous infusion of NGR-hTNF is characterized by onset of an early on-target adverse effect consisting of short-lived chills Methods: The impact of the onset of chills over treatment on the clinical outcome was assessed by a pooled analysis of individual patient data from 7 phase II trials. Dataset included 336 patients who had received NGR-hTNF 0.8 µg/m2 every 3 weeks (q3w) or weekly (q1w) as single agent (mesothelioma, colon and liver cancer) or combined with doxorubicin (ovarian cancer, sarcomas and SCLC) or with platinum-based regimen (NSCLC). In all trials, tumor response by RECIST criteria was assessed q6w until disease progression. To mitigate guarantee-time bias, onset of chills was treated as a time dependent covariate in Cox models fitted to estimate unadjusted and adjusted hazard ratios (HR). Endpoints of interest were progression free survival (PFS) and overall survival (OS). Median follow-up time was 26.9 months Results: 204 patients (61%) experienced chills on treatment, while 132 (39%) did not, with rates of all-grade events ranging from 40% to 76% among different trials (p=0.008). According to severity, 64% of patients had grade 1, 34% grade 2 and 2% grade 3. By timing of chills appearance, 88% occurred over the first six weeks and 12% later. Incidence was higher with q1w than with q3w dosing schedule (70% vs 56%; odds ratio, 1.78; p=0.02). Baseline characteristics (chills vs no-chills groups): median age, 63 vs 61; male, 58% vs 42%; PS ≥ 1, 67% vs 33%; prior lines ≥ 1, 66% vs 34%. Among baseline factors, logistic regression analysis retained only previous treatment associated with higher incidence of chills (odds ratio, 2.0; p=0.003). Onset of chills, used as a time-varying covariate, significantly correlated with improved PFS (HR=0.79; 95% CI, 0.69-0.91; p=0.001) in multivariable analysis adjusted for baseline factors and stratified on trial. Occurrence of chills remained also independently associated with better OS (HR=0.88; 95% CI, 0.79-0.99; p=0.03) Conclusions: Early onset of chills on treatment with NGR-hTNF may be associated with more prolonged clinical benefit Clinical trial information: NCT00994097 and others.
A Prospective Phase II Study of Thalidomide, Cyclophosphamide and Prednisone in Newly Diagnosed Idiopathic Multicentric Castleman's Disease
Authors: Lu Zhang, Ai-lin Zhao, Jun Feng, Xinxin Cao, Yan Zhang, Tienan Zhu, Minghui Duan, Daobin Zhou, Jian Li
Journal: Blood (2018)
Abstract 19555: Lifetime Risk of Heart Failure With Preserved Ejection Fraction and Heart Failure With Reduced Ejection Fraction: An Individual-Level Pooled Analysis
Authors: Ambarish Pandey, Wally Omar, Colby Ayers, Norrina Allen, Michael LaMonte, Liviu Klein, Lewis H Kuller, Philip Greenland, Charles Eaton, John S Gottdiener, Donald Lloyd-Jones, Jarett Berry
Journal: Circulation (2017)

Introduction: Lifetime risk of HF has been estimated to range from 20% to 46% in diverse sex and race groups. However, lifetime risk estimates for the two HF phenotypes, HFpEF and HFrEF, have not b...
Abstract P071: Moderate Exposure to Inorganic Arsenic in Drinking Water is Associated with Elevated Pulse Pressure: Results from Chihuahua, Mexico
Authors: Michelle A Mendez, Carmen González-Horta, Blanca Sánchez-Ramírez, Lourdes Ballinas-Casarrubias, Roberto Hernández Cerón, Damian Viniegra Morales, Francisco Andres Baeza Terrazas, Daniela Gutiérrez-Torres, María Cecilia Ishida, Zuzana Drobna, John Buse, Gonzalo G García-Vargas, Luz M. Del Razo, Miroslav Stýblo1
Journal: Circulation (2017)

Background: Though levels of arsenic &gt;100 μg/L in drinking water have been consistently associated with increased risk of cardiovascular disease (CVD), evidence of an association at lower levels of exposure is more inconsistent. We used data from a cohort from Chihuahua Mexico to examine whether relatively low levels of arsenic in drinking water were associated with elevated pulse pressure, a marker linked to arterial stiffening and CVD risk. Methods: We used concentrations of arsenic in household drinking water from 931 adults not taking hypertensive medication to examine the association between water arsenic categories as low as 25-50 μg/L and mean increases in systolic, diastolic and pulse pressure (systolic - diastolic pressure). We also examined the association between water arsenic categories and elevated pulse pressure, defined as &gt;70 mm Hg. Associations between arsenic exposure and blood pressure measures were obtained from multivariable linear or logistic regression models that adjusted for age, gender, education level, ethnicity, BMI, waist circumference, smoking status and alcoholic beverage intake. Results: After multivariable adjustment, compared to lower levels, water arsenic concentrations of 25-50 μg/L and above were associated with statistically significant increases in systolic blood pressure (SBP) and pulse pressure, but were not associated with diastolic blood pressure (DBP). Multivariable-adjusted associations [β (95% confidence interval)] with water arsenic concentrations of 25-50 μg/L were: 4.3 (1.2-7.4) mm Hg for SBP; 3.3 (0.8-5.7) mm Hg for pulse pressure; and 1.3 (-0.6-3.3) mm Hg for DBP. For elevated pulse pressure (16.1% of the sample), the association [odds ratio (95% CI)] with water arsenic levels of 25-50 μg/dL was 2.5 (1.3-4.9). Conclusions: Results support potential adverse effects of exposure to moderate levels of arsenic in drinking water on CVD risk through pathways that may involve widening pulse pressure.
Signaling Responses to Stroma-Derived Soluble Factors Are Associated with Outcome and with Expression of Microenvironment-Related Genes in Pediatric AML
Authors: Padmini Narayanan, Yi-Cheng Wang, Chris Tsz-Kwong Man, Rhonda E. Ries, Robert B Gerbing, Soheil Meshinchi, Todd A Alonzo, Michele Redell
Journal: Blood (2018)
Abstract 14079: Diagnostic Impact of the Finding From Study of Coronary Images in Acute Coronary Syndrome Patients With Out-of-Hospital Cardiac Arrest
Authors: Kazuya Tateishi, Daisuke Abe, Toru Iwama, Tatsuro Sassa, Kouichi Ohashi, Masakazu Kaneko, Tomohiko Harunari, Yoshiaki Yui, Norihiro Kuroki, Takao Yuba, Ko Suzuki, Yuichi Hamabe
Journal: Circulation (2015)

Background: Acute coronary syndrome (ACS) is the major cause of out-of-hospital-cardiac-arrest (OHCA). The patients with ventricular fibrillation (VF) have more chance to get the return of spontaneous circulation (ROSC) and favorite neurological outcome by using defibrillator compared with pulseless electrical activity (PEA) and asystole. The duration from collapse to ROSC is important in ACS patients with OHCA, but the relationship between the finding from study of coronary images and ROSC interval is still unknown. Objective: We investigated the association between the finding from study of coronary images and ROSC interval in ACS patients with OHCA. Methods: A cohort of 2779 patients was admitted to our emergency center due to cardiopulmonary arrest (CPA) from April 2011 to March 2015. We included the ACS patients who had CPA with VF as an initial rhythm, successfully resuscitated, underwent coronary angiography (CAG), had a culprit lesion, and needed percutaneous coronary intervention (PCI) (n=58, 63.7±12.0 years old, 93.1% male ). We divided the 58 patients into 2 groups; early ROSC group (ROSC ≦20min: E-ROSC n=24) and late ROSC group (ROSC &gt;20min: L-ROSC n=34), and analyzed their characteristics, respectively. Results: Age was no significant difference between 2 groups (E-ROSC vs. L-ROSC; 64.8±14.3 vs. 63.0±10.2, p=0.54). E-ROSC group had higher incidence of female (17% vs. 0%), successful resuscitation by defibrillator (96% vs. 21%), and higher 30 days survival rate (96% vs. 41%) compared with L-ROSC group (all p&lt;0.05). The finding of collateral artery for the culprit lesion: Rentrop I-III and TIMI III flow in CAG on arrival were no significant differences between 2 groups (Rentrop I-III : 45.8% vs. 55.9% P=0.45; TIMI III: 33% vs. 59% P=0.88). Incidence of multi-vessel disease was lower in E-ROSC than L-ROSC (16.7% vs. 58.9% P=0.001). Conclusion: Collateral and TIMI flow were not associated with ease of resuscitation, but multi-vessel disease may have a negative impact on resuscitation especially VF.
Safety and Tolerability of Lurbinectedin (PM01183) in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome
Authors: Kelly S. Chien, Christopher B. Benton, Ayalew Tefferi, José Rodríguez, Farhad Ravandi, Naval G. Daver, Elias J. Jabbour, Nitin Jain, Yesid Alvarado, Monica Kwari, Sherry A. Pierce, Abhishek Maiti, Marisa J Hornbaker, Margarida Almeida Santos, Sara Martinez, Mariano Siguero, Darci Zblewski, Aref Al-Kali, William J. Hogan, Hagop M. Kantarjian, Animesh Pardanani, Guillermo Garcia-Manero
Journal: Blood (2018)
Abstract 15431: Impact of Malnutrition as a Key Prognostic Factor in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Tetsuya Takahashi, Tetsu Watanabe, Taro Narumi, Takayuki Sugai, Taku Toshima, Miyuki Yokoyama, Daisuke Kinoshita, Satoshi Nishiyama, Hiroki Takahashi, Takanori Arimoto, Tetsuro Shishido, Takuya Miyamoto, Isao Kubota
Journal: Circulation (2015)

Background: Malnutrition is one of the unfavorable prognostic factors in patients with heart failure (HF). Prevalence of HF with preserved ejection fraction (PEF) (defined as left ventricular ejection fraction &gt;50%) has been increased and there is an obvious association between HF-PEF and hypertension, diabetes mellitus, and insulin resistance. However, association between malnutrition and clinical outcomes in patients with HFPEF remains to be elucidated. Methods and Results: We evaluated controlling nutritional status score (CONUT), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI) in 190 patients with HFPEF (mean 69.9 ± 11.6 years) admitted to our hospital. Patients were prospectively followed with the endpoints being cardiovascular death or rehospitalization. There were 56 events including 14 deaths and 42 rehospitalizations during a median follow-up of 14.0 months. Patients with cardiac events showed more severe New York Heart Association (NYHA) functional class and lower left ventricular ejection fraction (LVEF) compared with those without. Total lymphocyte count, serum albumin, and total cholesterol level were lower in patients with cardiac events. Patients with cardiac events showed higher CONUT score (6 vs 2, P&lt;0.001), lower PNI (30.4 vs 38.9, P&lt;0.001), and lower GNRI (84.9 vs 96.3, P&lt;0.001) compared with those who without. The correlations between each nutritional index and clinical parameters were examined. CONUT score, PNI, and GNRI correlated with age, LVEF, and serum brain natriuretic peptide (BNP) level. In Cox proportional hazards analysis, higher CONUT score (adjusted hazard ratio 9.0, 95% confidence interval (CI) 3.2-25.2), lower PNI (3.6, 1.7-7.7), and lower GNRI (6.3, 2.7-14.9) were independently associated with cardiac events after adjustment of age, gender, NYHA functional class, and serum BNP level. Kaplan-Meier analysis revealed that significantly higher cardiac event rate was observed in the patients with malnutrition (log-rank test, P&lt;0.001). Conclusion: Malnutrition was associated with unfavorable outcomes in patients with HFPEF. Evaluating nutritional status may provide valuable prognostic information in patients with HFPEF.
Pilot study of human papilloma virus in esophageal cancers.
Authors: P.U. Prakash Saxena, Anshul Singh, Rishanki Jha, Milan Joshi, Donald J. Fernandes, MS Vidyasagar
Journal: Journal of Clinical Oncology (2014)

e15059 Background: The role of HPV as one of the causative agents in oropharyngeal malignancies has been established. Evidence suggest that such cases may fare better than conventional head and and neck malignancies and for such subtypes dose de-escalation studies are already being conducted. The method of transmission is yet to be defined, most of the studies implicate oral sex (from mouth to-genital or mouth-to-anus contact).As esophagus is anatomically a continuous structure with the upper aero-digestive tract, we hypothesized that HPV may be associated with some esophageal cancers as well. Methods: 21 cases of squamous cell carcinomas esophagus treated with radical chemo-radiotherapy were included.Post treatment these patients were followed up every month for dysphagia assesment.The tissue biopsy sample preserved in wax block were sent for analysis. HYBRID DNA CAPTURE technique was used for identifying HPV DNA in the sample.The HPV types included in the test were: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68.A cut-Off Ratio of 0 to 0.99 is NEGATIVE for HR HPV; Cut-Off Ratio 1.0 or above is POSITIVE for HR HPV based upon the semi -quantitative viral load, represented as a numeric positive cut-off value. The cut-off ratio at 1.0 correspond to viral DNA load of ~5,000 copies/assay or 1 picogram/ml at a threshold of finding a clinical disease. Results: There were 10 male (47.61%) and 11 female patients (52.38%) with median age being 60 yrs. Out of 21 samples analyzed 9 were postive for high risk HPV DNA (42.8%), one was classified as borderline negative (4.76%). Out of positive samples 3 were males (33%) and 6 were females (66%). 77.77 % of the HPV positive group were non-smokers. 55 % of the HPV positive tumors (5/9) were located in the lower third of esophagus. 77.7% of HPV positive tumor patients had no evidence of dysphagia after 1 month of finishing treatment as compared to 66.6% of HPV negative tumors. Conclusions: This study shows that there may be a possible association between HPV viruses and esophageal cancers despite having small numbers. A possible association also may exist between non smokers and HPV. In future we plan to conduct studies where in addition to other predictive markers available for response assessment to chemo-radiation, HPV will also be tested.
Amrubicin monotherapy in patients with platinum-refractory metastatic neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma of the gastrointestinal tract.
Authors: Tomonori Araki, Tetsuya Hamaguchi, Atsuo Takashima, Yoshitaka Honma, Satoru Iwasa, Natsuko T. Okita, Ken Kato, Yasuhide Yamada, Hironobu Hashimoto, Hirokazu Taniguchi, Ryoji Kushima, Kazuhiko Nakao, Yasuhiro Shimada
Journal: Journal of Clinical Oncology (2014)

e15165 Background: Amrubicin (AMR), an anthracycline agent, has shown promise and a better safety profile compared with topotecan, as a second-line treatment for patients with small cell lung cancer (SCLC). However, there are few reports of AMR use in patients with metastatic neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC) of the gastrointestinal tract (GIT). We conducted a retrospective review to investigate the efficacy and safety of AMR in patients with GIT-NEC/MANEC refractory to platinum-based chemotherapy. Methods: Information on platinum-refractory GIT-NEC/MANEC patients, who received AMR monotherapy between February 2004 and July 2012 at the National Cancer Center Hospital, was collected from our database. AMR was administered intravenously as a 5-minute infusion, at a dose of 30–45 mg/m2 on days 1–3, and repeated every 3–4weeks. To determine pathological status, all patients were reclassified based on the 2010 WHO classification of neuroendocrine neoplasms of the digestive system. The overall response rate (RR) were evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, progression-free survival (PFS), overall survival (OS), and adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results: Twenty-one patients received AMR: 20 GIT-NEC and 1 GIT-MANEC patient. The median age was 63 years, with 17 males and 4 females. RR for 18 patients was 22.2% (95% CI, 3.0–41.4%), the median PFS was 3.7 months (95% CI, 2.6–4.8), and the median OS was 7.8 months (95% CI, 7.2–8.4). RR was calculated except for 3 cases which didn't have any target lesion. Grade 3/4 neutropenia occurred in 52.4% of patients, and febrile neutropenia or infection with Grade 3/4 neutropenia in 14.3%. Other non-hematologic toxicities, diarrhea, nausea, and vomiting were mild and no treatment-related deaths were observed. Conclusions: AMR displays tolerable toxicity and may enable treating platinum-refractory GIT-NEC/MANEC patientswith intermediate RR, PFS and OS. Further prospective evaluation of AMR for GIT-NEC/MANEC is warranted.