tbuckley/cabot-search huggingface dataset:
Risk factors for nodal metastasis in women with grade 3 endometrial cancer.
Authors: Leslie Horn Clark, Emily Meichun Ko, Victoria Lin Bae-Jump, Paola A. Gehrig
Journal: Journal of Clinical Oncology (2012)

e15511 Background: No studies have reported on the association of nodal metastases and lower uterine segment (LUS) in grade 3 endometrial cancer. Our study aimed to determine the frequency of nodal metastasis in these high-risk patients stratified by LUS involvement. Methods: A retrospective analysis was conducted on grade 3 endometrial cancer cases from 2005-2010. Statistical analyses were performed using summary frequencies and multivariate logistic regression analysis, with two-tailed p values of &lt;0.05 considered significant. Results: 329 cases were identified. 80.9% women underwent retroperitoneal node dissection, of whom 95.1% underwent pelvic (P) node dissection and 85.3% underwent periaortic (PA) node dissection. Of the women who had nodal dissection, mean age was 65.3 and BMI 31.1. Histology included 33.5% endometrioid, 49.3% serous or clear cell, and 15.4% carcinosarcoma. Stage distribution included 57.6% stage I, 8.0% stage II, 29.8% stage III, and 4.6% stage IV. Of LUS+ cases, 42% (56/132) had nodal metastases, in contrast to 12.7% (17/134) of LUS- cases. Sensitivity of + nodes by LUS was 76.6%, with a specificity of 60.6%, positive predictive value of 42.4%, and negative predictive value of 87.3%. Of LUS+ cases, 49/123 (39.8%) had +P nodes; 27/106 (21.8%) +PA nodes; and 21/100 (21%) had both +P/PA nodes. Of LUS- cases, 15/130 (11.5%) had +P nodes; 7/121 (5.8%) +PA nodes; and 4/121(3.3%) had both +P/PA nodes. Confirming the above findings, when adjusting for myometrial invasion and lymphovascular invasion, overall nodal status, +P nodal status and PA nodal status were independently associated with LUS (p&lt;0.000; p=0.001; p=0.003 respectively). Conclusions: There is debate regarding the utility of lymph node assessment in women with endometrial cancer. However, women with grade 3 endometrial cancer are at high risk for nodal involvement. This information is critical in determining post-operative adjuvant therapy. This data suggests women with grade 3 endometrial cancer, particularly those with lower uterine segment involvement, should undergo routine lymphadenectomy due to the high risk of nodal involvement.
Do people always invest less in attack than defense? Possible qualifying factors
Authors: Ori Weisel
Journal: Behavioral and Brain Sciences (2019)

Abstract In many conflict situations, defense is easier to mobilize than attack. However, a number of factors, namely, the initial endowments available to each side, the stakes of the conflict, the respective costs of defense and attack, and the way that conflict is framed and perceived, may make attacking more attractive than defending.
Zoledronic acid (ZA) to prevent bone loss during combined androgen blockade with finasteride (CAB+F) for clinically localized or recurrent non-osseous prostate cancer (PC)
Authors: S. Tucker, S. Binder RN, C. Chua RN, A. C. Houts PhD, B. V. Fortner PhD, L. S. Schwartzberg
Journal: Journal of Clinical Oncology (2006)

14628 Background: Androgen suppression (AS) is increasingly used as primary therapy for early PC and recurrent PSA-only PC. AS decreases bone mineral density (BMD), increases markers of osteoclastic and osteoblastic activity, and increases fracture risk. CAB+F is a maximal form of AS which has not been described in prospective trials. We present the first analysis of a prospective study of ZA to prevent bone loss in men receiving CAB+F. Methods: We performed a prospective non-randomized study of ZA in men receiving CAB+F for non-osseous PC. CAB+F consisted of 48 weeks of an LH-RH agonist and antiandrogen (bicalutamide or flutamide) plus finasteride 5 mg QD. Men received ZA 4 mg intravenous at entry and every 3 months. Calcium 1000 mg and calcitriol 0.5 mcg were given QD. Baseline and serial measures of osteocalcin (OC) and deoxypyridinoline (DPD) were assayed. Baseline BMD of the lumbar spine (LS) was measured by DEXA. Quality of life (QOL) was measured with a validated symptom-based scale for pen-based computers. Results: From 7/2004 through 12/2005, 26 men with PC met eligibility criteria and enrolled. ECOG status at entry was 0 for all. Mean age was 64 (range 46–81), mean PSA was 10.6 ng/mL (range 3.23–33.0) and median Gleason sum (GS) was 7 (range 5–9). Mean testosterone was 455 ng/dL. High risk PC (PSA &gt; 20, or GS &gt; 7, or T3 stage) was seen in 7/26 men. In preliminary analysis of men completing 48 weeks of CAB+F (n = 13), mean (±SD) LS BMD (gm/cm 2 ) increased significantly from 1.245 (±0.170) to 1.425 (±0.198) (p = 0.002). Baseline mean OC (ng/ml) decreased from 7.69 (±0.20) to 2.50 (±1.48) and baseline mean DPD (nmol/mmol Cr) decreased from 6.75 (±5.72) to 4.20 (±2.03). All men achieved PSA &lt; 0.1 by 24 weeks. Serial QOL data is significant for decreased sexual interest and mild fatigue compared with baseline. No grade 3 or 4 toxicities were seen. Expanded QOL and toxicity data will be described. Conclusion: ZA given at baseline and every 3 months in conjunction with maximal AS, CAB+F, significantly improves BMD of the lumbar spine and suppresses biochemical markers of both bone resorption and formation. No significant financial relationships to disclose.
Influence of pH on the activity of finafloxacin against extracellular and intracellular Burkholderia thailandensis, Yersinia pseudotuberculosis and Francisella philomiragia and on its cellular pharmacokinetics in THP-1 monocytes
Authors: H. Chalhoub, S.V. Harding, P.M. Tulkens, F. Van Bambeke
Journal: Clinical Microbiology and Infection (2019)
Evaluation of gefitinib biological effects in patients with solid tumors amenable to sequential biopsies—Final results
Authors: P. Kulesza, J. R. Brahmer, A. Jimeno, S. D. Baker, A. Spitz, J. Li, M. A. Rudek, W. A. Messersmith, M. Hidalgo
Journal: Journal of Clinical Oncology (2006)

3090 Background: Biological effects of gefitinib are not well understood. The goals of this study are to assess the effects of gefitinib on EGFR signaling pathways in tumor and normal tissue, as well as the relationship between pharmacologic and pharmacodynamic (PD) endpoints. Methods: Patients (pts) with a diagnosis of a solid tumor and amenable to serial biopsies received gefitinib in two sequential cohorts of 12 pts each at doses of 250 or 500 mg orally once a day. Biopsies of tumor and skin as well as plasma and oral buccal swabs were collected at baseline and 28 days after treatment for correlative studies. Plasma samples for pharmacokinetic studies were obtained on d1 (from 0–8h), and pre-treatment trough samples were obtained on d2, d3, d8, d15, d22, and d28 of cycle 1. Treatment was continued unless severe drug related toxicity developed or until disease progression. Results: 27 pts (15 M/12F; median age of 61, range 29–77) were treated (13 on 250 mg and 14 on 500 mg). Three pts withdrew prior to d28 biopsy. One pt with metastatic squamous cell skin cancer had a partial response (PR). Of the 4 pts with stable disease (SD) (2-carcinoid, 1-lung, 1-renal), the median time on study was 6 mo (range 3–7 mo). Grade 1–3 toxicities included rash, diarrhea, nausea, anorexia, and fatigue. Plasma exposure to gefitinib was highly variable. At 250 mg, gefitinib average pre-treatment trough concentrations (Css,min) during 28 days of treatment varied 19-fold (mean, 406 ng/ml; range, 104 to 1846 ng/ml); at 500 mg, Css,min varied 11-fold (mean, 502 ng/ml; range, 145 to 1590 ng/ml). Quantitative immunohistochemical staining revealed a correlation between a lower baseline level of tumor Ki-67 and benefit from treatment (PR + SD) (p=0.048). While the change in tumor pMAPK staining (change from baseline) was not different between the two dose levels, Ki-67 change trended greater in the pts on the 500 mg dose (p=0.06). Change from baseline in pMAPK correlated with the development of diarrhea (p=0.03). EGFR (CA) repeat polymorphism length was not related to treatment benefit, toxicity, or changes in pMAPK or Ki-67. Conclusions: The preliminary PD findings are provocative. Further testing of tumor and normal tissues is ongoing. [Table: see text]
Modulation of the transcriptional activation functions of estrogen receptor and androgen receptor by cofactor of BRCA1 (COBRA1)
Authors: Jian-Long Sun, Ashley Blair, Sarah Aiyar, Rong Li
Journal: Cancer Research (2006)

2321  Estrogen receptor (ER) and androgen receptor (AR) play pivotal roles in the cancer development in hormone-responsive tissues including breast and prostate. The transcriptional potency of these steroid hormone receptors is dictated by a combinatorial action of transcriptional coactivators and corepressors, most of which exert their regulatory functions at the stage of transcriptional initiation. We have recently discovered that cofactor of BRCA1 (COBRA1), a component of the four-subunit negative elongation factor (NELF), interacts with estrogen receptor α (ERα). Together with the other subunits of NELF, COBRA1 inhibits estrogen-dependent transcription by stalling RNA polymerase II (RNAPII) during transcription elongation. This new level of regulation may constitute part of the mechanisms that control the duration and magnitude of a rapid and reversible hormonal response. As an extension of the original study, we now demonstrate that, in addition to ERα, COBRA1 is also physically associated with androgen receptor (AR), progesterone receptor B (PR B), and glucocorticoid receptor (GR). Among these steroid hormone receptors, AR appears to have the highest binding affinity for COBRA1. Domain-mapping studies suggest that the ligand-binding domain (LBD) of AR interacts with multiple regions of COBRA1. Reduction of COBRA1 level by siRNA significantly increases androgen-dependent transcription in an MMTV-LTR reporter assay. We also evaluated the impact of COBRA1 on the transcription of several endogenous androgen-responsive genes by quantitative RT-PCR. Interestingly, both androgen-dependent and -independent transcription of these genes are augmented when COBRA1 level is reduced by siRNA. Preliminary data indicate that COBRA1 may modulate AR-mediated transcription by influencing its transcriptional activity as well as protein abundance. The biological significance of the COBRA1-mediated transcriptional repression in hormone-responsive tissues is under active investigation.
Control of DU145 and LNCaP-LN3 prostate cancer spheroid growth using Bi-213-labeled multiple targeted alpha radioimmunoconjugates
Authors: Jian Wang, Syed M. Abbas Rizvi, Paul J. Cozzi, Michele C. Madigan, Chang F. Qu, Berry J. Allen, Pamela J. Russell, Yong Li
Journal: Cancer Research (2005)

1468  Purpose: Metastatic disease is a major problem for prostate cancer (CaP) patients. Defining the expression of tumor-associated antigen (TAAs) or receptors on CaP will enable selection of therapeutic targets. Because of the heterogeneous expression of targeted antigens, multi-targeted therapy may increase the likelihood of complete targeting of micro-metastatic disease. This study aims to test multiple target expression (uPA, MUC1 BLCA-38) on fresh human CaP tissues and cultured spheroids, and to target DU 145 and LNCaP-LN3 CaP spheroids with different TAA expression levels using Bi-213-labeled multiple targeted alpha radioimmunoconjugates. Methods: The expression of uPA, MUC1 and BLCA-38 on CaP spheroids from DU 145 and LNCaP-LN3 cell lines was detected by immunohistochemistry and flow cytometry. Test and control alpha conjugates (ACs) were prepared using two monoclonal antibodies (MAbs), an inhibitor, plasminogen activator inhibitor type 2 (PAI2) that binds to the cell-membrane-bound protease, urokinase plasminogen activator (uPA), and control protein labelled with Bi-213 using standard methodology. Spheroids of DU 145 and LNCaP-LN3 CaP cell lines were incubated with different activities of test and control ACs, and spheroid growth was measured by light microscopy over a 50-day period. Results: The TAAs were expressed heterogeneously on frozen sections from human CaP tissues. The DU 145 cancer spheroids expressed antigens that bind MAbs BLCA-38, C595 and #394 (mouse anti-human uPA B-chain) while LNCaP-LN3 cancer spheroids bound C595 but not BLCA-38 or #394. The activity concentration required to yield a 50% reduction in spheroid volume at day 35 post-inoculation related to controls was 12.6 uCi/mL and 52.3 uCi/mL in the multiple alpha conjugates( test) for DU 145 and LN3 spheroids respectively. Conclusion: Prostate cancer-associated antigens recognised by multiple MAbs are potential targets for alpha therapy. Multiple targeted alpha therapy (MTAT) can produce cytotoxicity specific to two CaP spheroids and may be a potent therapeutic agent against metastatic prostate cancer cells exhibiting intermediate to high target antigen expression, overcoming the heterogeneity of expression of targeted antigens. Supported by US Army Medical Research and Material Command (Award No: W81XWH-04-1-0048)
A randomized trial evaluating the integration of online questionnaires into follow-up (FU) care for early-stage breast cancer (ESBC).
Authors: Alyse Wheelock, Meredith Bock, Eva Mihalis, Nancy Shepard, Dan H. Moore, Mary Lou Ernest, Hope S. Rugo, Laura Esserman, Michelle E. Melisko
Journal: Journal of Clinical Oncology (2012)

9107 Background: Large numbers of cancer survivors have led to the need for FU care addressing lasting effects of BC and its treatment. We conducted a trial evaluating formats of FU care to determine if integration of remote electronic questionnaire FU provides for timely symptom management and more efficient care than routine clinic visits alone. Methods: Patients (pts) with ESBC were randomized to either usual care (UC, frequency of visits determined by oncology providers) with completion of an optional online health and symptom questionnaire (Q) before each clinic visit, or to SIS.NET FU care, in which pts were scheduled for up to 3 routine oncology related clinic visits over 18 mos and completed the online Q every 3 mos. Qs were reviewed by a survivorship nurse practitioner (NP) with pt phone contact for symptoms requiring urgent attention. We recorded the time between electronic symptom reporting and FU for pts in the SIS.NET arm. Data included the number of oncology related clinic visits, total number of physician visits, and number of medical tests including labs and imaging studies ordered. Kolmogorov-Smirnov tests for equal distributions were used to determine if there were any significant differences between SIS.NET and UC. Results: 100 pts were enrolled, 75 completed the 18 month study and 25 pts remain in FU. For the 75 pts, 85% received chemotherapy and 77% received hormone therapy. Pts in the SIS.NET arm completed an average of 3.8 out of 7.2 emailed surveys (52.6%), and pts in the UC arm completed an average of 2.2 out of 3.4 (69.1%) routine pre-clinic surveys. For pts in the SIS.NET arm, 75% of reported symptoms were reviewed by a NP in &lt; 3 days. There was no significant difference between SIS.NET and UC FU for oncology related clinic appointments, total number of physician visits, or number of medical tests performed. Conclusions: Use of on-line health and symptom surveys with remote NP review provided timely symptom FU but did not reduce clinic visits or medical testing in pts with ESBC. Further analyses of these data as well as additional studies are necessary to understand the barriers to integration of web-based tools to achieve more efficient FU care for BC survivors.
Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis and a history of nonsteroidal immunosuppressant use: a post hoc analysis of the phase III CAFE trial
Authors: Bouaziz J-D., G Ogg, M de Bruin-Weller, T Bieber, A Irvine, B Shumel, J Msihid, A B Rossi
Journal: British Journal of Dermatology (2019)
SINEUP Non-coding RNA Targeting GDNF Rescues Motor Deficits and Neurodegeneration in a Mouse Model of Parkinson’s Disease
Authors: Stefano Espinoza, Margherita Scarpato, Devid Damiani, Francesca Managò, Maddalena Mereu, Andrea Contestabile, Omar Peruzzo, Piero Carninci, Claudio Santoro, Francesco Papaleo, Federico Mingozzi, Giuseppe Ronzitti, Silvia Zucchelli, Stefano Gustincich
Journal: Molecular Therapy (2019)

Glial cell-derived neurotrophic factor (GDNF) has a potent action in promoting the survival of dopamine (DA) neurons. Several studies indicate that increasing GDNF levels may be beneficial for the treatment of Parkinson's disease (PD) by reducing neurodegeneration of DA neurons. Despite a plethora of preclinical studies showing GDNF efficacy in PD animal models, its application in humans remains questionable for its poor efficacy and side effects due to its uncontrolled, ectopic expression. Here we took advantage of SINEUPs, a new class of antisense long non-coding RNA, that promote translation of partially overlapping sense protein-coding mRNAs with no effects on their mRNA levels. By synthesizing a SINEUP targeting Gdnf mRNA, we were able to increase endogenous GDNF protein levels by about 2-fold. Adeno-associated virus (AAV)9-mediated delivery in the striatum of wild-type (WT) mice led to an increase of endogenous GDNF protein for at least 6 months and the potentiation of the DA system's functions while showing no side effects. Furthermore, SINEUP-GDNF was able to ameliorate motor deficits and neurodegeneration of DA neurons in a PD neurochemical mouse model. Our data indicate that SINEUP-GDNF could represent a new strategy to increase endogenous GDNF protein levels in a more physiological manner for therapeutic treatments of PD. Glial cell-derived neurotrophic factor (GDNF) has a potent action in promoting the survival of dopamine (DA) neurons. Several studies indicate that increasing GDNF levels may be beneficial for the treatment of Parkinson's disease (PD) by reducing neurodegeneration of DA neurons. Despite a plethora of preclinical studies showing GDNF efficacy in PD animal models, its application in humans remains questionable for its poor efficacy and side effects due to its uncontrolled, ectopic expression. Here we took advantage of SINEUPs, a new class of antisense long non-coding RNA, that promote translation of partially overlapping sense protein-coding mRNAs with no effects on their mRNA levels. By synthesizing a SINEUP targeting Gdnf mRNA, we were able to increase endogenous GDNF protein levels by about 2-fold. Adeno-associated virus (AAV)9-mediated delivery in the striatum of wild-type (WT) mice led to an increase of endogenous GDNF protein for at least 6 months and the potentiation of the DA system's functions while showing no side effects. Furthermore, SINEUP-GDNF was able to ameliorate motor deficits and neurodegeneration of DA neurons in a PD neurochemical mouse model. Our data indicate that SINEUP-GDNF could represent a new strategy to increase endogenous GDNF protein levels in a more physiological manner for therapeutic treatments of PD.
Association of Childhood Maltreatment With Interpersonal Distance and Social Touch Preferences in Adulthood
Authors: Ayline Maier, Caroline Gieling, Luca Heinen-Ludwig, Vlad Stefan, Johannes Schultz, Onur Güntürkün, Benjamin Becker, René Hurlemann, Dirk Scheele
Journal: American Journal of Psychiatry (2019)

Objective: Childhood maltreatment is a major risk factor for psychopathology associated with interpersonal problems in adulthood, but the etiological pathways involved are still unclear. The authors propose that childhood maltreatment confers risk for dysfunctional behavior in social interactions by altering interpersonal distance preference and the processing of social touch. Methods: Ninety-two medication-free adults (64 of them female) with low, medium, and high levels of childhood maltreatment were tested with an interpersonal distance paradigm and subsequently underwent a social touch functional MRI task during which they rated the perceived comfort of slow touch (C-tactile [CT] optimal speed; 5 cm/s) and fast touch (non-CT-optimal speed; 20 cm/s). Results: Participants with high childhood maltreatment levels preferred a larger interpersonal distance and experienced fast touch as less comforting compared with participants with no or moderate childhood maltreatment experiences. On the neural level, participants with severe childhood maltreatment exhibited exaggerated responses to fast touch in the right somatosensory and posterior insular cortex, which correlated with lower comfort ratings. Severe childhood maltreatment was associated with decreased activation in the right hippocampus in response to slow touch. This response pattern was not moderated or mediated by childhood maltreatment–associated region-specific reductions in gray matter volume. Conclusions: The study findings suggest that higher childhood maltreatment levels are associated with hypersensitivity characterized by a preference for larger interpersonal distance and discomfort of fast touch. These dysregulations were manifested in a sensory cortical hyperreactivity and limbic CT-related hypoactivation. These results may shed light on why individuals with severe childhood maltreatment exhibit an increased susceptibility to interpersonal dysfunctions and psychiatric disorders in adulthood.
CT FFR for Ischemia-Specific CAD With a New Computational Fluid Dynamics Algorithm
Authors: Chun Xiang Tang, Chun Yu Liu, Meng Jie Lu, U. Joseph Schoepf, Christian Tesche, Richard R. Bayer, H. Todd Hudson, Xiao Lei Zhang, Jian Hua Li, Yi Ning Wang, Chang Sheng Zhou, Jia Yin Zhang, Meng Meng Yu, Yang Hou, Min Wen Zheng, Bo Zhang, Dai Min Zhang, Yan Yi, Yuan Ren, Chen Wei Li, Xi Zhao, Guang Ming Lu, Xiu Hua Hu, Lei Xu, Long Jiang Zhang
Journal: JACC. Cardiovascular imaging (2019)