tbuckley/cabot-search huggingface dataset:
Prognostic impact of C-reactive protein kinetics for advanced renal cell carcinoma treated with sunitinib.
Authors: Tetsuo Fujita, Ken-ichi Tabata, Daisuke Ishii, Kazumasa Matsumoto, Kazunari Yoshida, Masatsugu Iwamura
Journal: Journal of Clinical Oncology (2015)

e15602 Background: Sunitinib is widely approved for the treatment of advanced renal cell carcinoma (RCC). The need to identify biomarkers predicting the efficacy of sunitinib is urgent. We previously revealed that pretreatment normal C-reactive protein (CRP) predicts better oncological outcomes of sunitinib. However, CRP kinetics of sunitinib have never been described. In the cytokine era, CRP kinetics have an impact on survival in patients with metastatic RCC. As such, in the present study, we evaluate CRP kinetics in advanced RCC patients treated with sunitinib. Methods: Between December 2008 and 2012, 56 consecutive patients with advanced RCC treated with sunitinib were enrolled in the present study. Patients were divided into 3 cohorts according to the pretreatment CRP level and CRP kinetics: (i) normal CRP cohort; defined as pretreatment CRP level ≤ 0.30 mg/dL, (ii) normalized CRP cohort; defined as pretreatment CRP > 0.30 mg/dL and normalized CRP level within 2 cycles of treatment, (iii) non-normalized CRP cohort; defined as pretreatment CRP > 0.30 mg/dL and not normalized CRP after the initiation of sunitinib. Disease control rates, nonparametric estimates of progression-free survival and overall survival were evaluated. Effects of selected variables on survival were assessed by means of multivariate regression with the Cox proportional hazards model. Results: The normal and normalized CRP cohorts showed statistically significant better disease control rates than the non-normalized CRP cohort (P = 0.0002). The normal CRP cohort showed significantly longer progression-free survival than the non-normalized CRP cohort (median 19.0 months vs 5.0 months, P = 0.0050). The normal and normalized CRP cohorts showed significantly longer overall survival than the non-normalized CRP cohort (median 32.0 and 26.0 months vs 11.0 months, P = 0.0005 and 0.0466, respectively). On multivariate analysis, normal plus normalized CRP was a predictor of better overall survival (P= 0.0084). Conclusions: CRP kinetics is a prognostic indicator as well as pretreatment CRP level in patients with advanced RCC treated with sunitinib.
Abstract P218: Eating Frequency, Breakfast Consumption, and Abdominal Obesity Among Adults Living in Puerto Rico
Authors: Martha Tamez, Josiemer Mattei
Journal: Circulation (2019)

Background: Puerto Rican adults have a high burden of obesity, but little information is available regarding eating frequency and breakfast consumption in this at-risk ethnic minority group. Thus, we examined the association between eating frequency, breakfast consumption, and abdominal obesity among adults living in Puerto Rico. Methods: In a cross-sectional study of adults living in Puerto Rico aged 30-75 years old (n=310) were asked to self-report eating frequency, including snacks. Trained interviewers measured waist (WC) and hip circumferences. We calculated the waist-to-hip ratio (WHR) by dividing the waist by the hip measurement. Abdominal obesity was defined as either high WC (men≥94 cm; women≥80 cm) or high WHR (men≥0.90; women≥0.85), using International Diabetes Federation cutoffs. Odds ratios (ORs) and 95% confidence intervals (95% CIs) of having abdominal obesity by frequency of meals (≤1.5; 1.5-3; ≥3 times/d) and for breakfast consumers (vs. non) were estimated using logistic regression models. We adjusted for age, sex, income, smoking status, physical activity, TV watching, energy intake, diet quality, and eating frequency (only for breakfast consumption). Results: The majority of the participants consumed breakfast (70%), ate 1.5-3 times/d (47%), had high WC (75%), and had high WHR (77%). Higher frequency of eating was associated with higher WC after adjustment for confounders. Compared with participants who ate ≤1.5 times/d, those who ate 1.5-3 times/d were more likely to have a higher WC (OR: 2.75, 95% CI: 1.23, 6.15) and those who ate ≥3 times/d were more likely to have an increased WC (OR: 2.88; 95%CI: 1.14, 7.31; P-trend=0.04). Breakfast consumption was not significantly associated with abdominal obesity. Conclusions: Higher frequency of eating, but not breakfast consumption by itself, was significantly associated with abdominal obesity. Our study denotes which eating behaviors may be more relevant for abdominal adiposity among a high-risk ethnic group.
Outcomes of stereotactic ablative radiotherapy for extra-cranial oligo-metastatic renal cell cancer.
Authors: Yuanyuan Zhang, Jonathan Schoenhals, Alana Christie, Chiachien Wang, Osama Mohamad, Nirmish Singla, Neil Desai, Hak Choy, Kevin Dale Courtney, Aditya Bagrodia, Vitaly Margulis, I. Alex Bowman, Robert D. Timmerman, James Brugarolas, Raquibul Hannan
Journal: Journal of Clinical Oncology (2019)

599 Background: Stereotactic ablative radiotherapy (SAbR) is a standard of care for treating renal cell cancer (RCC) cranial metastasis. We describe the effect of SAbR on oligometastatic extra-cranial RCC disease course. Methods: We retrospectively reviewed 49 patients with oligometastatic RCC with 68 extra-cranial lesions. Patients were treated with SAbR with a curative intent from 2007 to 2017. We analyzed local control, systemic therapy free survival (mPFS), and overall survival. Results: With a median follow-up of 28 months (IQR: 16.0-40.3), the 1-year and 2-year overall survival after SAbR was 93.4% (95% CI: 81.0-97.8), and 83% (95% CI: 67.4-91.5) respectively. The median overall survival was not reached. The median time to systemic therapy was 13.4 months from the first SAbR(95% CI: 8.8-27.6). Median times from the first SabR course to second and third line systemic therapy (or death) were 31.8 months and 45 months, respectively. Patients in the favorable risk group by the Heng’s criteria (HR = 8.67, p = 0.04), with nometastatic disease at diagnosis (HR = 10.38, p &lt; 0.01) and with clear cell histology (HR = 6.15, p &lt; 0.01) exhibited better survival, as shown by univariate analysis. Patients with no metastatic disease at diagnosis (HR = 2.56, p = 0.02) and only one metastasis treated with SAbR (HR = 2.36, p = 0.03) also exhibited better systemic therapy-free survival. SAbR had an excellent local control rate of 94% at 2 years with no reported grade 3 or higher toxicity. Conclusions: SAbR is an effective and safe treatment for oligometastatic RCC, offering excellent local control with minimal toxicity. SAbR delayed the start of systemic therapy for this RCC cohort, offering quality of life benefits for patients without adversely affecting the progression on subsequent lines of systemic therapy. These findings call for prospective verification.
Intra-vesical therapy using 4N1K-peptide in bladder cancer and its effects on tumor growth and angiogenesis.
Authors: Yasuyoshi Miyata, Kyohei Araki, Tsutomu Yuno, Yuichiro Nakamura, Yuji Sagara, Tomohiro Matsuo, Kojiro Ohba, Hideki Sakai
Journal: Journal of Clinical Oncology (2019)

446 Background: The 4N1K-peptide (KRFYVVMWKK), which is derived from thrombospondins has anti-cancer activities in several cancers. We previously found that 4N1K-peptide expression was negatively associated with tumor invasion and prognosis in patients with bladder cancer (BC). The main aim of this study is to clarify whether intravesical therapy using 4N1K-peptide has anti-cancer effects in BC by in vivo and in vitro studies. Methods: Change in tumor growth and apoptosis due to transfection of 4N1K-peptide were evaluated in the BC cell line, T24 cells. Next, to clarify the anti-cancer effects of 4N1K-peptide as intra-vesical therapy, cell survival, apoptosis, and microvessel density (MVD) were investigated in chemical (BBN)-induced BC mouse model. In this study, natural saline (Ns) and 4NGG-peptide which has a similar structure to 4N1K-peptide but does not have any biological activity were used. In addition, survival analyses are performed in these mouse model. Results: In T24 cells, mean/SD of AI in 4N1K-peptide-transfected cells was 7.9/1.1%, which was remarkably higher (P &lt; 0.001) than that in 4NGG-peptide-transfected cells (1.6 / 0.2%). In mouse model, 7 of the 20 mice treated with Ns died because of cancer-related symptoms, and invasive cancer was detected in 9/13 (69.2%). In contrast, in mice treated with 4N1K-peptide, 1 of 15 mice was died and invasive disease was observed in 1/14 (7.1%) at 24 weeks of age. Kaplan-Meier survival cures showed mice treated with 4N1K-intarvesical therapy had better prognosis compared to others (P = 0.036). In mouse tissues, apoptotic index in mice treated with 4N1K-peptide was significantly higher (P &lt; 0.01) than that in others. In contrast, MVD in mice with 4N1K-peptide was significantly lower (P &lt; 0.05) compared to others. In normal urothelium of mouse treated with 4N1K-peptide, change of morphological characteristics was not detected. Conclusions: 4N1K-peptide played as tumor-suppressor by regulating apoptosis and angiogenesis in BC animal model. Therefore, there is the possibility that 4N1K-peptide is a potential useful and safety therapeutic agent for intra-vesical therapy in BC patients.
Cetuximab or Panitumumab versus Bevacizumab in the treatment of first line RAS wild type colorectal cancer: pooled analysis of randomized clinical trials.
Authors: Emiliano Tamburini, Britt Rudnas, Mario Nicolini, Stefania Nicoletti, Manuela Fantini, Claudio Ridolfi, Carlotta Santelmo, Lucia Stocchi, Paolo Fabbri, Eleonora Barzotti, Fabrizio Drudi, Maximilian Papi, Lorenzo Gianni, Davide Tassinari
Journal: Journal of Clinical Oncology (2015)

e14634 Background: To assess the role of anti-EGFR agents [Cetuximab (C) or Panitumumab(P)] or Bevacizumab (B) in the treatment of RAS wild type metastatic colorectal cancer. Methods: The final results of 3 randomized phase III trials comparing anti-EGFR agents with B in the treatment of RAS wild type metastatic colorectal cancer were computed in a pooled analysis. Overall Survival in K-RAS wild type patients treated with anti-EGFR agents vs B was the primary end point of the trial; overall survival in the sub-groups of ALL-RAS patients treated with anti-EGFR agents vs B, and K-RAS or ALL-RAS patients treated with C vs B were the secondary ones. Primary and secondary end points were assessed as Hazard Ratio (HR) and 95% Confidence Interval (95CI). Heterogeneity between the trials was assessed using the I2 test; the outcome analysis was performed using a random effects model with an alpha error of 5%. Results: We analyzed the outcomes of 2014 K-RAS wild type patients treated with B vs anti-EGFR agents, 1096 ALL-RAS wild type patients treated with B vs anti-EGFR agents, 1729 K-RAS wild type patients treated with B vs C, and 926 ALL-RAS wild type patients treated with B vs C. A large to moderate heterogeneity was observed in all the analyses with I2 values of 76%, 27%, 59% and 49%, respectively. The pooled Hazard Ratio in the four analyses was 0.798 (95CI: 0.658-0.967, p = 0.021), 0.763 (95CI: 0.61-0.955, p = 0.018), 0.853 (95CI: 0.704-1.034, p = 0.106), and 0.794 (95CI: 0.633-0.997, p = 0.047), respectively. Conclusions: Our data, although preliminary and extracted from heterogeneous trials, seem to suggest a superiority of anti EGFR agents in the treatment of RAS wild type metastatic colorectal cancer. It follows that anti-EGFR agents should probably be considered the treatment of choice in the subgroup of patients with metastatic RAS wild type colorectal cancer.
Abstract 13090: Extremely Poor Prognosis after Cardiac Resynchronization Therapy is Predictable by Heterogeneous Multi-directional Left Ventricular Activation Sequence on Magnetocardiography
Authors: Takahiro Nakashima, Hiroshi Takaki, Shogo Oishi, Shunsuke Usami, Kohei Ishibashi, Ikutaro Nakajima, Yuko Yamada, Koji Miyamoto, Hideo Okamura, Takashi Noda, Takeshi Aiba, Shiro Kamakura, Hideaki Kanzaki, Wataru Shimizu, Toshihisa Anzai, Satoshi Yasuda, Kengo Kusano, Masaru Sugimachi
Journal: Circulation (2013)

Backgrounds: Cardiac resynchronization therapy (CRT) provides no benefit in an approximately one third of the patients with advanced heart failure, that is not readily predictable by any clinical tool. We hypothesized that multi-channel magnetocardiography (MCG) capable of delineating ventricular activation sequence can identify heterogeneous (multi-directional) left ventricular (LV) intraventricular conduction, which would predict non-responders to CRT and poor outcomes after CRT implantation. Methods: We analyzed 64-Ch MCGs (1kHz) in 56 patients with advanced HF (LVEF 24±8%) and QRS duration (146±30ms) on ECG before CRT implantation. According to the QRS current arrow mapping of MCG, they were divided into Group-U (n=35) with uni-directional homogeneous ventricular conduction (UDC) and Group-M (n=21) with multi-directional heterogeneous ventricular conduction (MDC). CRT responder was defined when LVESV decreased >15% or LVEF increased >15%. Results: Baseline LVEF and NYHA class were comparable between t...
A Disinhibitory Microcircuit Mediates Conditioned Social Fear in the Prefrontal Cortex
Authors: Haifeng Xu, Ling Liu, Yuanyuan Tian, Jun Wang, Jie Li, Junqiang Zheng, Hongfei Zhao, Miao He, Tian-Le Xu, Shumin Duan, Han Xu
Journal: Neuron (2019)
PARP-1 regulation of DNA repair factor availability.
Authors: Matthew Joseph Schiewer, Amy C Mandigo, Nicolas Gordon, Christopher McNair, Costas D. Lallas, Edouard John Trabulsi, Benjamin Leiby, Karen E. Knudsen
Journal: Journal of Clinical Oncology (2019)

269 Background: PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Previously, it was determined that PARP-1 ins involved in regulation of androgen receptor activity. Methods: Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP-1 enzymatic activity.Results: Further investigation of the PARP-1-regulated transcriptome and secondary strategies for assessing PARP-1 activity in patient tissues revealed that PARP-1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double-strand breaks, suggesting that enhanced PARP-1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP-1 served to enhance E2F1 transcription factor activity, and specifically promoted E2F1-mediated induction of DNA repair factors involved in homologous recombination (HR). Conversely, PARP-1 inhibition reduced HR factor availability and thus acted to induce or enhance “BRCA-ness”. Conclusions: These observations bring new understanding of PARP-1 function in cancer and have significant ramifications on predicting PARP-1 inhibitor function in the clinical setting.
The significance of insulin receptor expression to predict the resistance to VEGFR-TKIs and induce PD-L1 expression in advanced clear cell renal cell carcinoma.
Authors: Masayuki Takahashi, Kei Daizumoto, Tomoya Fukawa, Yayoi Fukuhara, Keisuke Ozaki, Megumi Tsuda, Yoshito Kusuhara, Hidehisa Mori, Yasuyo Yamamoto, Kunihisa Yamaguchi, Tomoharu Fukumori, Hiroomi Kanayama
Journal: Journal of Clinical Oncology (2019)

592 Background: Previously we have identified the prognostic gene set of ccRCC patients, where insulin receptor (INSR) expression was decreased in the patients with poor outcome (Proc Natl Acad Sci U S A., 2001). We examined the clinical significance of decreased INSR expression and sought to elucidate the underlying mechanisms. Methods: The INSR expression was immunohistochemically examined in the nephrectomy specimens of RCC patients (n = 33) who then received axitinib. We established patient derived Xenograft model (PDX) of ccRCC and examined the INSR expression in the axitinib resistant PDX tumors by Western blotting. As the INSR is expressed in the vascular endothelial cells, we co-cultured the RCC cell lines with the human renal glomerular endothelial cells (HGEC) treated with si-RNA of INSR (si-INSR) and the microarray experiment was conducted. Results: In RCC patients with axitinib, those with low INSR expression had poor outcome (median PFS 19.5 vs 2.3 months, p &lt; 0.001; median OS 34.2 vs 5.6 months, p = 0.001). The INSR expression was the significantly independent predictor of PFS (p = 0.006). In the axitinib-resistant PDX tumors, the expression of INSR was decreased. In the co-culture experiments, the microarray experiments revealed that the decreased INSR expression in the HGECs may be involved with the important signaling pathway including interferon response in Caki-1 cells. Interferon- β was highly expressed in HGECs with si-INSR. The decreased INSR expression and the increased interferon-β expression in HGEC were confirmed when axitinib was administered. The Caki-1 cells that was co-cultured with HGECs treated with si-INSR demonstrated high expression of PD-L1. The PD-L1 expression was increased in a concentration-dependent manner of recombinant interferon-β and increased phosphorylation of STAT1 and STAT3 were observed. Conclusions: In conclusion, the decreased INSR expression could be a biomarker to predict the resistance to VEGFR-TKIs. The decreased INSR expression was correlated with the increased interferon-β expression in HGECs, which leads to the induction of PD-L1 through increased phosphorylation of STAT1 and STAT3.
Препараты висмута в гастроэнтерологической практике
Authors: Yu.M. Stepanov, N.Yu. Zavhorodnia, O.Yu. Lukianenko
Journal: GASTROENTEROLOGY (2019)

В статье на основании обзора литературных данных проанализированы механизмы антихеликобактерной и цитопротективной активности соединений висмута. Представлена характеристика роли препаратов висмута в современных схемах эрадикации, а также приведены результаты собственных исследований эффективности и безопасности применения коллоидного субцитрата висмута в составе антихеликобактерной терапии второй линии у детей.
Long term survival of gemcitabine and cisplatin followed by radiation in advance head and neck cancer.
Authors: Hassan Iqbal, Arif Jamshed, Raza Hussain, Sumayya Hameed
Journal: Journal of Clinical Oncology (2015)

e17083 Background: In this retrospective study we evaluated the response, efficacy, toxicity and long term follow-up of patients treated with gemcitabine and cisplatin followed by radiation or chemo-radiation (RT/CRT) in non metastatic advance head and neck cancer. Methods: A total of 446 patients were included in this study treated from 2005 – 2009 in our institution. Pretreatment AJCC stage; T1-3 N0/N+ 139 (31%), T4 N0/N+ 307 (69%). All patients received gemcitabine 1 gm /m2 (day 1, 8) and cisplatin 75 mg/m2 (day1 only). This cycle was repeated every 3 weeks followed by radiation from 55 – 70 Gy in 20 – 35 fractions respectively. 383 (86%) patients received 2 cycles of induction chemotherapy (IC). A total of 299 (67%) patients received concurrent 3 weekly cisplatin (75 mg/m2). Patient characteristics included; Male: female 2:1, Median age 50 years. Site; oral cavity 232 (52%), hypopharynx 45 (10%), nasopharynx 63 (14%), larynx 46 (10%), oropharynx 14 (3%), paranasal sinuses 33 (8%) and others 13 (3%). Histological diversity; squamous cell carcinoma 373 (84%), undifferentiated carcinoma 53 (12%), others 20 (4%). Results: Response to IC: complete response (CR) 58 (13%), partial response (PR) 315 (71%), stable disease (SD) 55 (12%) and progressive disease (PD) 18 (4%). Response to RT/CRT; CR 293 (66%) and persistent disease at 3 months post treatment in 153 (34%) patients. G3/G4 toxicity for induction chemotherapy was anemia 2%/0%, neutropenia 17%/4%, thrombocytopenia 2%/1%, vomiting 5%/1% and diarrhea 5%/1%. G1 transient elevation of ALT/ AST was 17% /11%. G3/4 elevation of creatinine was 2 %/1%. Nine patients (2%) had toxicity related hospital admissions during RT/CRT. The 5 and 10 year OS, DFS and RFS were 56%, 53%, 45%, 41%, 30% and 27% respectively. 149 (33%) patients are alive, disease free and maintaining routine follow up. Conclusions: The long term follow up of our study with comparable survival outcomes and acceptable toxicity merits further evaluation in randomized trials.
Abstract P349: Psychosocial Resources and Stressors Associated With Cognition Among Middle-Aged and Older Hispanics/Latinos: Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study
Authors: Mayra L Estrella, Melissa Lamar, Ramon Durazo-Arvizu, Wassim Tarraf, Carmen R Isasi, Krista M Perreira, Maria J Marquine, Richard B Lipton, Hector M González, Linda C Gallo, Martha L Daviglus
Journal: Circulation (2019)

Introduction: Evidence suggests that psychosocial factors, e.g., resources and stressors, are associated with cognitive function and risk for dementia in non-Latino Whites and Blacks. Less is known about the associations between psychosocial factors and cognitive function among Hispanics/Latinos, a group at high risk for dementia. Hypothesis: Psychosocial resources ( ethnic identity , familism , family cohesion , life engagement , optimism , social network embeddedness , and social support ) will be positively associated, and stressors ( ethnic discrimination , loneliness , and subjective social status ) negatively associated with global cognition [GC] and individual test scores for verbal learning, memory, verbal fluency, and processing speed. Methods: Data from the parent HCHS/SOL and its SCAS were used (N = 2,792; ages 45-74). Cognitive function was assessed using standardized tests and GC score was derived from individual test scores. Psychosocial factors were self-reported; higher scores indicate greater levels. Cross-sectional associations between each psychosocial factor and cognition were examined using weighted linear regression models adjusted for age, sex, Hispanic/Latino background, income, education, depressive symptoms, field center, high cholesterol, hypertension, diabetes, obesity, smoking, diet quality, and physical activity. Results: In final models (see Table 1), ethnic identity , life engagement , and social support were positively associated with GC, and familism and loneliness were negatively associated with GC. Family cohesion , optimism , social network embeddedness , ethnic discrimination , and subjective social status were not associated with GC. Life engagement and social support were positively associated with all individual test scores. Conclusions: Life engagement and s ocial support may be particularly important psychosocial resources for cognitive health among Hispanics/Latinos. Longitudinal associations and their underlying mechanisms should be explored.
Probing Computation in the Primate Visual System at Single-Cone Resolution
Authors: A. Kling, G.D. Field, D.H. Brainard, E.J. Chichilnisky
Journal: Annual Review of Neuroscience (2019)

Daylight vision begins when light activates cone photoreceptors in the retina, creating spatial patterns of neural activity. These cone signals are then combined and processed in downstream neural circuits, ultimately producing visual perception. Recent technical advances have made it possible to deliver visual stimuli to the retina that probe this processing by the visual system at its elementary resolution of individual cones. Physiological recordings from nonhuman primate retinas reveal the spatial organization of cone signals in retinal ganglion cells, including how signals from cones of different types are combined to support both spatial and color vision. Psychophysical experiments with human subjects characterize the visual sensations evoked by stimulating a single cone, including the perception of color. Future combined physiological and psychophysical experiments focusing on probing the elementary visual inputs are likely to clarify how neural processing generates our perception of the visual world.