tbuckley/cabot-search huggingface dataset:
Effect of methionine-depletion via methioninase-treatment on cancer cells in S/G2 phase and chemosensitivity.
Authors: Shuya Yano, Shukuan Li, Qinghong Han, Yuying Tan, Michael Bouvet, Toshiyoshi Fujiwara, Robert M. Hoffman
Journal: Journal of Clinical Oncology (2015)

e13512 Background: A major impediment to the response of tumors to chemotherapy is that the large majority of cancer cells within a tumor are quiescent in G0/G1, where cancer cells are resistant to chemotherapy. Methods: To attempt to solve this problem of quiescent cells in a tumor, cancer cells were treated with recombinant methioninase (rMETase), which selectively traps cancer cells in S/G2 by depletion of methionine for which cancer cells have an elevated requirement (Expert Opin. Biol. Ther. 15, 21-31, 2015). The cell-cycle phase of the cancer cells was visualized with the fluorescence ubiquitination cell cycle indicator (FUCCI). At the time of rMETase-induced S/G2-phase blockage, identified by the cancer cells’ green fluorescence by FUCCI imaging, the cancer cells were administered S/G2-dependent chemotherapy drugs, which interact with DNA or block DNA synthesis such as doxorubicin, cisplatin, or 5-fluorouracil. Results: Treatment of cancer cells with drugs only, without rMETase-induced S/G2 phase blockage, led to the majority of the cancer-cell population being blocked in G0/G1 phase, identified by the cancer cells becoming red fluorescent in the FUCCI system. The G0/G1 blocked cells were resistant to the chemotherapy. In contrast, trapping of cancer cells in S/G2 phase by rMETase treatment followed by FUCCI-imaging-guided chemotherapy was highly effective in killing the cancer cells. Conclusions: Trapping of cancer cells in S/G2 increases their chemosensitivity and rMETase is a good candidate for trapping cancer cells in S/G2 to greatly increase chemosensitivity.
Advanced Phases at Diagnosis of Childhood Chronic Myeloid Leukemia : The Experience of the International Registry for Chronic Myeloid Leukemia (CML) in Children and Adolescents (I-CML-Ped Study)
Authors: Frédéric Millot, Joelle Guilhot, Meinolf Suttorp, Natacha Maledon, Meral Günes Adalet, Petr Sedlacek, Eveline S. de Bont, Chi Kong Li, Krzysztof Kalwak, Birgitte Lausen, Gordana Jakovljevic, Michael Dworzak, Andrea Hraskova, Barbara De Moerloose, Roula Farah, Andrea Biondi, Andre Baruchel
Journal: Blood (2017)
The value of AKR1C3 in predicting the therapeutic efficacy of abiraterone for patients with metastatic castration-resistant prostate cancer.
Authors: Jinge Zhao
Journal: Journal of Clinical Oncology (2019)

313 Background: AKR1C3 is a multifunctional enzyme playing a significant role in androgen synthesis and metabolism. Previous studies have proved that the activation of AKR1C3 was associated with resistance to abiraterone through increasing the intracrine androgen synthesis. However, clinical validation is still lacking as to the prognostic value of AKR1C3 in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone. Methods: Data of 117 patients with mCRPC between 2016-2018 in our center were retrospectively analyzed. AKR1C3 was detected by the immunohistochemical staining from the 12-core prostate biopsy. Kaplan-Meier curves and COX regression were used to analyze the association between AKR1C3 and the treatment outcomes of abiraterone. The endpoints of this study were PSA progression-free survival (PSA-PFS) and radiograph progression-free survival (rPFS). Results: In total, AKR1V3 was detected in 40/117 (34.2%) cases. The positive AKR1C3 was significantly associated with shorter PSA-PFS for mCRPC patients treated with abiraterone (median PSA-PFS: 6.2 Mo vs. 11.1 Mo, p &lt; 0.001). Those with positive AKR1C3 were also accompanied with obviously poorer rPFS compared to those with negative AKR1C3 staining, despite that the difference was not statistically significant (median rPFS: 11.1 Mo vs. 21.8 Mo, p = 0.250). Multivariate COX regression indicated that, AKR1C3 was an independent prognosticator of rapid PSA progression for the abiraterone treatment (HR,95%CI: 2.612, 1.54-4.44, p &lt; 0.001). Conclusions: This is the first study verifying the adverse prognostic significance of AKR1C3 for mCRPC patients receiving abiraterone treatment. Our results suggested that, AKR1C3 was closely related to early treatment failure of abiraterone, and thus, was worthwhile to be routinely described in pathological report.
AB0028 The serum levels of soluble icam-1, nitric oxide and xanthine oxidase in rheumatoid arthritis
Authors: A Erdal, K Senel, S Taysi
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> This study was carried out to determine the serum levels of soluble intercellular adhesion molecule 1 (ICAM-1), nitric oxide and xanthine oxidase in patients with rheumatoid arthritis (RA) and to investigate the correlations between sICAM-1 and nitric oxide and xanthine oxidase. <h3>Methods</h3> Serum samples were obtained from 30 patients with active RA and 20 healthy control subjects. sICAM-1, nitric oxide and xanthine oxidase levels were determined. <h3>Results</h3> sICAM-1, nitric oxide and xanthine oxidase levels were significantly elevated in patients with RA (p &lt; 0.001). We found a significant positive correlation between s ICAM-1 and nitric oxide (r = 0.426, p &lt; 0.05). There was also a significant positive correlation between s ICAM-1 and xanthine oxidase (r = 518, p &lt; 0.01). <h3>Conclusion</h3> High levels of s ICAM 1 may be a a consequence of inflammation or tissue damage made by nitric oxide generated by xanthine oxidase.
Abstract P126: The Cardiovascular Health of Afro-Caribbean Immigrants in New York City: a Cross Sectional Study
Authors: Sabena Thomas, Amna Umer, Yvonne Commodore-Mensah, Sumaira Khalid, Christiaan Abildso
Journal: Circulation (2019)

Introduction: Afro-Caribbean (AC) immigrants are the largest black immigrant group in the U.S. and generally display better physical health than United States (U.S.) born blacks. Cardiovascular health (CVH) disparities among AC immigrant sub-groups are poorly understood. We examined the prevalence of CVH factors among AC immigrants (Guyanese, Haitian and Jamaican) relative to U.S. born blacks residing in New York City. We hypothesized that some AC immigrant sub-groups will have higher rates of CVH factors than U.S. born blacks. Methods: We performed a cross-sectional analysis of pooled data from the 2010-2014 New York City Community Health Survey administrations to estimate the prevalence of CVH and differences among AC immigrant sub-groups. We included 7678 non-Hispanic black participants from Haiti (n=291), Jamaica (n=1031), Guyana (n=369) and U.S. born blacks (5987). Logistic regression was used to examine the association between country of birth and CVH factors. The CVH factors were determined from the AHA’s CVH metrics. We adjusted the models for significant covariates using backward sequential selection. Results: In final adjusted models, in comparison to U.S. born blacks, Jamaican immigrants were more likely to self-report diabetes but were less likely to be overweight/obese. Guyanese immigrants were also less likely to be overweight/obese than U.S. born blacks. There were no significant differences between Haitian immigrants and U.S. born blacks for CVH factors. Conclusions: Although AC immigrants depict superior health status compared to U.S. born blacks, ethnic differences exist in CVH among AC immigrant sub-groups. Efforts to address cardiovascular health factors among black populations in the U.S. should consider ethnic differences that may provide information about the most at-risk populations for disease-specific programmatic or policy interventions.
Abstract MP27: The Association Between Psychosocial Factors and Sleep Among African-American Men and Women, the Jackson Heart Sleep Study
Authors: Dayna A Johnson, Na Guo, Tené T Lewis, Tamar Sofer, David R Williams, Mario Sims, James G Wilson, Susan Redline
Journal: Circulation (2019)

Background: Emerging evidence suggests that sleep traits and disorders are strong predictors of cardiovascular disease (CVD), particularly among African-Americans. Identifying determinants of insufficient sleep among African-Americans may help to target interventions and potentially reduce CVD burden. Psychosocial factors may be particularly relevant to sleep health among African-Americans; however, more research is needed using objective and well-validated sleep assessments. We investigated associations of individual and aggregate psychosocial factors (e.g. stress, depression, anxiety) with objectively-measured sleep traits and insomnia; and examined differences by sex among African-Americans. Methods: Between 2012 and 2016, Jackson Heart Sleep Study (JHSS) participants (N=913) underwent 7-day wrist actigraphy, had a clinic visit and completed questionnaires. Actigraphy-based measures included short sleep duration (&lt;6 hours), low sleep efficiency (&lt; 85%), and wake after sleep onset (WASO). Insomnia was assessed by the Women’s Health Initiative Insomnia Rating Scale (WHIIRS ≥10). A composite psychosocial factors variable was created based on the number of high-level factors that the participant reported: top quintile of stress (Perceived Stress Scale ≥ 18), high depressive symptoms (Center for Epidemiologic Studies Depression Scale-20, excluding restless sleep, ≥ 16), and top quintile of anxiety (State-Trait Anxiety Inventory score ≥ 38). Linear and logistic regression models were fit to test associations between psychosocial factors and sleep outcomes, adjusted for demographics, socioeconomic status, body mass index (BMI), and physical activity. Psychosocial factors and sex interactions were tested in adjusted models. Results: JHSS participants had a mean age of 63.4 years (standard deviation: 10.7), 33.6% were male, 53.6% had a college degree and the mean BMI was 31.9 kg/m 2 (6.9). Short sleep and low sleep efficiency were common, 26.1% and 30.0%, respectively. The average WASO was 54.5 (23.5) minutes. Psychosocial factors (composite and individually) were associated with insomnia. Adverse psychosocial factors were associated with a higher odds of insomnia, adjusted odds ratio (aOR)=1.65 (95% confidence interval: 1.39, 1.95). High anxiety, but not stress or depressive symptoms were associated with a short sleep duration, aOR=2.00 (1.34, 2.98). There was no evidence of associations between psychosocial factors and sleep efficiency or WASO in the overall sample. However, in males only, high anxiety and stress were associated with lower sleep efficiency, P ≤0.05 for all. Conclusion: Stress and negative emotional state, anxiety and depressive symptoms were associated with insomnia. Short sleep duration was specifically associated with anxiety. Psychosocial factors may be a point of intervention for improving sleep health, particularly among men.
Abstract P096: Factors Related to Added Sugars Intake Among US Adults With or Without Cardiovascular Diseases
Authors: Seung Hee Lee-Kwan, Elizabeth Lundeen, Sandra L Jackson, Heidi M Blanck, Sohyun Park
Journal: Circulation (2019)

Added sugars intake increases risk of obesity, hypertension, dyslipidemia, and cardiovascular diseases (CVD) and may impact disease management. We examined factors related to added sugars intake among US adults with or without CVD and risk factors using 2015 National Health Interview Survey (NHIS) (n=30616). NHIS used the National Cancer Institute (NCI) Dietary Screener Questionnaire (DSQ) to assess individual’s dietary intake. The DSQ used 8 questions to assess added sugar intake over the last 30 days. We used the NCI’s scoring algorithm to convert screener responses to estimate total added sugars intake (tsp/day) by characteristics within 3 strata—adults with a history of heart disease/stroke (CVD, n=4658), adults with hypertension/high cholesterol but without CVD (HTHC, n=10476), and adults without CVD or HTHC (no CVD, n=15482). Because our goal was not to look at association between added sugar and CVD risk, comparisons among the groups were not made. Characteristics included age, sex, race/ethnicity, education, income, marital status, smoking, and weight status. We used multiple linear regression to assess independent associations between intake and characteristics. Added sugars intake was similar in magnitude across all 3 strata (CVD 16.9, HTHC 17.0, and no CVD 17.3 tsp, respectively). We found increased added sugars intake with younger age, lower education, lower income, and smoking among adults regardless of CVD status. Having obesity was positively related to increased intake for adults without CVD, but no association was found between the weight status and intake in adults with CVD or HTHC. Improving diet may prevent CVD and aid disease self-management. Product reformulation to reduce added sugars and strategies to counsel and support individuals to reduce dietary added sugars may be needed to optimize heart health.
Abstract P215: Adherence to the Healthy Eating Index-2015 May Reduce the Risk of Incident Cardiovascular Disease, Cardiovascular Disease Mortality, and All-Cause Mortality
Authors: Emily A Hu, Lyn M Steffen, Josef Coresh, Lawrence J Appel, Casey M Rebholz
Journal: Circulation (2019)

Background: The Healthy Eating Index-2015 (HEI-2015) score measures adherence to recommendations from the most recent Dietary Guidelines for Americans . The HEI-2015 was altered from the HEI-2010 by replacing the empty calories component with saturated fat and added sugar. Few studies have examined the association between the HEI-2015 score and incident cardiovascular disease (CVD), CVD mortality, and all-cause mortality. Hypothesis: We hypothesized that a higher HEI-2015 score, indicating better diet quality, would be associated with a lower risk of incident CVD, CVD mortality, and all-cause mortality. Methods: We conducted a prospective analysis of 12,135 participants aged 45-64 years from the Atherosclerosis Risk in Communities (ARIC) study. The HEI-2015 score (0-100) was computed using the average dietary intake assessed using food frequency questionnaires at visits 1 (1987-89) and 3 (1993-95) and divided into quintiles. Incident CVD, CVD mortality, and all-cause mortality were ascertained from baseline through December 31, 2016. We conducted Cox proportional hazards models adjusted for covariates to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: There were 4,163 cases of incident CVD, 1,429 cases of CVD mortality, and 5,173 cases of all-cause mortality over a median of 25 years of follow-up. Compared to participants in the lowest quintile of HEI-2015 score, participants in the highest quintile had a 12% lower risk of incident CVD (HR: 0.88, 95% CI: 0.79-0.98), 41% lower risk of CVD mortality (HR: 0.59, 95% CI: 0.49-0.71), and 25% lower risk of all-cause mortality (HR: 0.75, 95% CI: 0.69-0.83) after adjusting for covariates ( Table ). There were significant trends across quintiles of HEI-2015 score for all three outcomes. Results were consistent by subgroups (sex, smoking, diabetes, hypertension). Conclusions: Higher adherence to the Dietary Guidelines for Americans 2015-2020 may reduce the risk of incident CVD, CVD mortality, and all-cause mortality among middle-aged adults in the U.S.
Prevalence and influence on outcome of <i>Neuregulin- (NRG1), HER2/neu- </i>and<i> HER3</i>- expression in patients with metastatic colorectal cancer (mCRC) treated with irinotecan-based first-line regimens (FUFIRI vs. mIROX) in the FIRE 1-trial.
Authors: Arndt Stahler, Volker Heinemann, Clemens Albrecht Giessen, Andreas Schalhorn, Sebastian Stintzing, Ludwig Fischer von Weikersthal, Ursula Vehling-Kaiser, Martina Stauch, Detlef Quietzsch, Jens Neumann, Thomas Kirchner, Andreas Jung, Dominik Paul Modest
Journal: Journal of Clinical Oncology (2015)

e14609 Background: The epidermal growth factor receptor is frequently expressed in colorectal carcinoma and acts as therapeutic target in RAS wild-type mCRC. Although HER2/neu- and HER3-targeted agents are available, little is known about the role of these receptors in mCRC. Hence, we set out to explore the impact of HER2/neu- and HER3- receptor as well as their ligand’s neuregulin (NRG1) expression in patients with mCRC. Methods: NRG1, HER2 and HER3 expression was detected by immunostaining in 208 available tumors of patients with mCRC receiving 5-FU/LV plus irinotecan (FUFIRI) or irinotecan plus oxaliplatin (mIROX) as first-line treatment within a randomized trial (FIRE1). For NRG1-, HER2/neu and HER3-expression, Rüschoff-score for immunohistochemistry (IHC) was used (i.e. +++ and ++ vs. + and 0) (Rüschoff et al.: HER2 testing in gastric cancer: a practical approach. Modern Pathology, 25, 637-650. 2012.). Expression of NRG1, HER2/neu and HER3 was correlated with response, median progression-free survival (PFS) and median overall survival (OS). Results: NRG1 (low: 192 vs high: 16), HER2/neu (low: 178 vs high: 30) and HER3 (low: 69 vs high: 139) expression was assessed in all 208 patients. High vs low HER3 expression did not influence outcome (PFS: 7.1 vs 8.8 months, HR: 1.11 [95% CI: 0.82 – 1.50], p = 0.50; OS: 19.8 vs 21.1 months, HR: 0.95 [95% CI: 0.70 – 1.30], p = 0.75), neither did high compared to low HER2/neu expression (PFS: 7.7 vs 8.0 months, HR: 1.07 [95% CI: 0.71 – 1.60], p = 0.75; OS: 16.6 vs 21.1 months, HR: 1.13 [95% CI: 0.75 – 1.71], p = 0.57). High vs low NRG1 expression affected PFS (4.7 vs 8.2 months, HR: 2.45 [95% CI: 1.45 – 4.13], p = 0.001), but not OS (15.5 vs 20.7 months, HR: 1.33 [95% CI: 0.76 – 2.35], p = 0.32). Conclusions: High IHC-expression of NRG1, HER2/neu and HER3 was detected in 8%, 14% and 67% of tumors respectively. High NRG1-expression was associated with inferior PFS, while HER2/neu and HER3 did not correlate with outcome. Further research is required to identify diagnostic algorithms and to explore if HER2/neu- and HER3-receptors represent potential targets in the treatment of mCRC.
Combining the Number of Infectious Episodes and Interval of Chemotherapy to Transplantation May Predict a Transplant Outcome in Patients with Acute Myeloid Leukemia: A Retrospective Analysis of JALSG AML201 Study
Authors: Satoshi Kaito, Noriko Doki, Yuho Najima, Shigeki Ohtake, Hitoshi Kiyoi, Hiroyuki Fujita, Yasushi Miyazaki, Noriko Usui, Hirokazu Okumura, Koichi Miyamura, Emiko Sakaida, Atsushi Fujieda, Nagai Tadashi, Takahisa Yamane, Ohnishi Kazunori, Tomoki Naoe, Kazuteru Ohashi
Journal: Blood (2018)
Experience of a single Brazilian center on PSMA-PET in biochemical recurrence in patients with prostate cancer.
Authors: Paulo Sergio Lages, Luciano Prado Junior, Leonardo Prado, Luciana Lages
Journal: Journal of Clinical Oncology (2019)

134 Background: Biochemical recurrence in prostate cancer is a common event, and we have data showing that PSMA-PET may guide therapy when it happens. Objectives: Verify the sensibility of PSMA-PET on biochemically recurrent prostate cancer and correlate it with PSA level and Gleason score. Methods: From October 2015 to August 2018, 547 PSMA-PET (68Ga-PSMA) was performed to evaluate prostate cancer individuals. 276 patients had already been treated from prostate cancer and were in biochemical recurrence. From these patients, 122 had information regarding Gleason Score. Results: From the 276 patients, we found 216 positive exams (78.3%). What we can see, and according to the present data we already have, is that the positivity rises with increasing PSA level. Conclusions: PSMA-PET is a useful strategy for planning treatment in patients with biochemical recurrent prostate cancer. The sensibility varies according to PSA level and Gleason Score. An interest thing observed is that the sensibility for Gleason 3+4 is similar to Gleason 3+3 and the sensibility for Gleason 4+3 is similar to 4+4, showing that the Gleason 7 disease has different behaviors, as previous shown in other trials. This dataset reinforces the importance of incorporating PSMA-PET in clinical practice.[Table: see text][Table: see text][Table: see text]
Double ligation-assisted endoscopic submucosal resection for wider-margin resection of nonmuscularis propria subepithelial esophageal lesions
Authors: Vincent Zimmer, Bert Bier, Frank Lammert
Journal: Endoscopy (2019)

Esophageal subepithelial lesions (SELs) are common in endoscopy practice. Clinical management depends on multiple factors including tissue diagnosis and, thus, assessment of malignant potential [1]. With respect to endoscopic resectability and, if appropriate, choice of therapeutic modality, characterization of the layer of origin is critical. However, as conventional low-frequency endosopic ultrasound (EUS) may not reliably determine the origin of a muscularis mucosae lesion, for example, clear-cut differentiation of the muscularis propria and nonmuscularis propria localization is more relevant. From this perspective, apart from granular cell tumors, which have a high rate of tissue diagnosis on standard forceps biopsy, EUS puncture is often discussed, but is also often technically complicated in small-sized lesions. Therefore, a more straightforward approach in easy-to-resect nonmuscularis propria lesions may be more appropriate, given adequate patient counseling and preference. Here, a novel variant technique, which is an evolution of endoscopic submucosal resection with ligation (ESMR-L) and is designated “double ligation-assisted endoscopic submucosal resection” (ESMR-DL), for rapid wide-margin removal of small SELs is presented in three consecutive patients [2] [3].
Pulmonary hypertension associated with left heart disease: efforts to improve the meaning of haemodynamic phenotypes
Authors: Juan C. Grignola, Pedro Trujillo, Enric Domingo
Journal: European Respiratory Journal (2019)

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