tbuckley/cabot-search huggingface dataset:
Measuring Self-Reported Cancer-Related Cognitive Impairment: Recommendations From the Cancer Neuroscience Initiative Working Group
Authors: Ashley M Henneghan, Kathleen Van Dyk, Tara Kaufmann, Rebecca Harrison, Christopher Gibbons, Cobi Heijnen, Shelli R Kesler
Journal: JNCI Journal of the National Cancer Institute (2021)

Cancer and its treatments are associated with increased risk for cancer-related cognitive impairment (CRCI). Methods and measures used to study and assess self-reported CRCI (sr-CRCI), however, remain diverse, resulting in heterogeneity across studies. The Patient-Reported Outcomes Working Group has been formed to promote homogeneity in the methods used to study sr-CRCI. In this report, using a psychometric taxonomy, we inventory and appraise instruments used in research to measure sr-CRCI, and we consider advances in patient-reported outcome methodology. Given its psychometric properties, we recommend the Patient-Reported Outcome Measurement Information System Cognitive Function Short Form 8a for measurement of sr-CRCI in cancer patients and survivors, at a minimum, to increase scientific rigor and progress in addressing CRCI.
Abstract PD10-04: Prognostic significance of germline BRCA mutations in patients with HER2-positive breast cancer. Epidemiological analysis in primary BRCA screens
Authors: Alessandro Viansone, Claudia Omarini, Daniela Boggiani, Angelica Sikokis, Vera Uliana, Benedetta Pellegrino, Federico Piacentini, Maria Michiara, Antonino Musolino
Journal: Cancer Research (2021)

Abstract Background: HER2-amplified breast cancers are rare amongst BRCA mutation carriers. No data exist regarding clinico-histological characteristics and prognosis of this subgroup of patients. Materials and Methods: Using a retrospective matched cohort design, we collected data from 728 women who were diagnosed with breast cancer from January 2006 to December 2016 and were screened for germline BRCA mutations. Clinical and histological characteristics of the primary tumor, time to relapse, and survival were analyzed by BRCA and HER2 status. Results: One hundred and twenty HER2-positive, BRCA mutated cases were evaluated with respect to three control groups: HER2-positive, BRCA wild-type (n=136); HER2-negative, BRCA-mutated (n=226); HER2-negative, BRCA wild-type (n=246). Breast cancers with hormone receptor-negative status or high histologic grade (odds ratio=1.7; 95% confidence interval [CI]: 1.0-2.9) were more likely HER2-positive, with no restriction by BRCA mutation status. Disease-free and overall survival for HER2-positive, BRCA mutated cases were lower than those for the other subgroups. An interaction between BRCA mutations and HER2-positive status was found for poorer overall survival after adjusting for prognostic variables (HR = 3.4; 95% CI: 1.3-16.7). Conclusions: Germline BRCA mutations confer worse prognosis in patients with HER2-positive breast cancer. Ongoing trials testing novel therapeutic approaches (e.g. anti-HER2 therapies combined with PARP inhibitors) are warranted. Citation Format: Alessandro Viansone, Claudia Omarini, Daniela Boggiani, Angelica Sikokis, Vera Uliana, Benedetta Pellegrino, Federico Piacentini, Maria Michiara, Antonino Musolino. Prognostic significance of germline BRCA mutations in patients with HER2-positive breast cancer. Epidemiological analysis in primary BRCA screens [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-04.
Modulation of the PI3K/Akt/mTOR signaling pathway by probiotics as a fruitful target for orchestrating the immune response
Authors: Amir Hossein Mohseni, Vincenzo Casolaro, Luis G. Bermúdez-Humarán, Hossein Keyvani, Sedigheh Taghinezhad-S
Journal: Gut Microbes (2021)

The mammalian target of rapamycin (mTOR) and the phosphatidylinositol-3-kinase (PI3K)/protein kinase B or Akt (PKB/Akt) signaling pathways are considered as two but somewhat interconnected significant immune pathways which play complex roles in a variety of physiological processes as well as pathological conditions. Aberrant activation of PI3K/Akt/mTOR signaling pathways has been reported to be associated in a wide variety of human diseases. Over the past few years, growing evidence in in vitro and in vivo models suggest that this sophisticated and subtle cascade mediates the orchestration of the immune response in health and disease through exposure to probiotics. An expanding body of literature has highlighted the contribution of probiotics and PI3K/Akt/mTOR signaling pathways in gastrointestinal disorders, metabolic syndrome, skin diseases, allergy, salmonella infection, and aging. However, longitudinal human studies are possibly required to verify more conclusively whether the investigational tools used to understand the regulation of these pathways might provide effective approaches in the prevention and treatment of various disorders. In this Review, we summarize the experimental evidence from recent peer-reviewed studies and provide a brief overview of the causal relationship between the effects of probiotics and their metabolites on the components of PI3K/Akt/mTOR signaling pathways and human disease.
Developmental programming of oxytocin through variation in early-life stress: Four meta-analyses and a theoretical reinterpretation
Authors: Bruce J. Ellis, Alexander J. Horn, C. Sue Carter, Marinus H. van IJzendoorn, Marian J. Bakermans-Kranenburg
Journal: Clinical Psychology Review (2021)

Despite evidence supporting a role for oxytocin (OT) in regulating social behavior, surprisingly little is known about how this neuropeptide is calibrated during development. We systematically reviewed empirical studies in humans (k = 86 publications reporting on 66 independent samples; N = 7319) that examined associations between early-life stress and three OT system components: endogenous OT, methylation of the OT receptor gene (OXTRm), and biological and behavioral responses to intranasally administered OT. In a series of meta-analyses, we found some evidence that people who grew up under more adverse conditions tend to have lower endogenous OT (children: r = .12; adults: r = .09), that early adversity is associated with higher levels of OXTRm (r = .02), and that adults who report lower levels of childhood adversity tend to show more positive responses to intranasally administered OT (r = .12). These results were found in typical populations, and were in most cases absent in clinical samples. We discuss these findings in terms of both the prevailing medical model (focusing on the harmful effects of early-life stress) and the adaptive calibration model (focusing on developmental adaptation of biobehavioral systems to early conditions) and suggest that an adaptation-based approach could meaningfully advance research and intervention on the sequelae of early adversity.
Asparagine couples mitochondrial respiration to ATF4 activity and tumor growth
Authors: Abigail S. Krall, Peter J. Mullen, Felicia Surjono, Milica Momcilovic, Ernst W. Schmid, Christopher J. Halbrook, Apisadaporn Thambundit, Steven D. Mittelman, Costas A. Lyssiotis, David B. Shackelford, Simon R.V. Knott, Heather R. Christofk
Journal: Cell Metabolism (2021)
Insufficient Radiofrequency Ablation Promotes Hepatocellular Carcinoma Metastasis Through N6‐Methyladenosine mRNA Methylation‐Dependent Mechanism
Authors: Tianhong Su, Manling Huang, Junbin Liao, Shuibin Lin, Peng Yu, Jianhua Yang, Yuhong Cai, Shenghua Zhu, Lixia Xu, Zhenwei Peng, Sui Peng, Shuling Chen, Ming Kuang
Journal: Hepatology (2021)

The dynamic N6-methyladenosine (m6 A) mRNA modification is essential for acute stress response and cancer progression. Sublethal heat stress from insufficient radiofrequency ablation (IRFA) has been confirmed to promote HCC progression; however, whether m6 A machinery is involved in IRFA-induced HCC recurrence remains open for study.Using an IRFA HCC orthotopic mouse model, we detected a higher level of m6 A reader YTH N6-methyladenosine RNA binding protein 1-3 (YTHDF1) in the sublethal-heat-exposed transitional zone close to the ablation center than that in the farther area. In addition, we validated the increased m6 A modification and elevated YTHDF1 protein level in sublethal-heat-treated HCC cell lines, HCC patient-derived xenograft (PDX) mouse model, and patients' HCC tissues. Functionally, gain-of-function/loss-of-function assays showed that YTHDF1 promotes HCC cell viability and metastasis. Knockdown of YTHDF1 drastically restrains the tumor metastasis evoked by sublethal heat treatment in tail vein injection lung metastasis and orthotopic HCC mouse models. Mechanistically, we found that sublethal heat treatment increases epidermal factor growth receptor (EGFR) m6 A modification in the vicinity of the 5' untranslated region and promotes its binding with YTHDF1, which enhances the translation of EGFR mRNA. The sublethal-heat-induced up-regulation of EGFR level was further confirmed in the IRFA HCC PDX mouse model and patients' tissues. Combination of YTHDF1 silencing and EGFR inhibition suppressed the malignancies of HCC cells synergically.The m6 A-YTHDF1-EGFR axis promotes HCC progression after IRFA, supporting the rationale for targeting m6 A machinery combined with EGFR inhibitors to suppress HCC metastasis after RFA.
Abstract 15512: Predictors of Normalization of Left Ventricular Systolic Function After Acute Myocarditis -multicenter Observational Study
Authors: Ayano Yoshida, Kentaro Jujo, Eiji Shibahashi, Takuma Takada, Yuichiro Minami, Chihiro Saito, Ashihara Kyomi, Nobuhisa Hagiwara
Journal: Circulation (2020)

Introduction: The clinical presentation of acute myocarditis is highly variable, and its prognosis is occasionally unpredictable. Even the patients discharge alive, left ventricular (LV) remodeling occurs during the follow-up period in some cases, which causes the progression of dilated cardiomyopathy or sudden cardiac death. Purpose: We aimed to investigate the predictors of the recovery of LV ejection fraction (LVEF) in patients with acute myocarditis. Methods: This multicenter observational study included 20 patients [average age 38 years, 18 (90%) male] suffering acute myocarditis who were urgently hospitalized between 2007 and 2019. Enrolled patients were assigned into 2 groups depending on a recovery of LV function that was defined as LVEF ≥55% by transthoracic echocardiography (TTE) within 12 months after the onset; the Recovery group (n=8) and Non-recovery group (n=12). Results: Overall, LVEF increased from 37% to 52% (p&lt;0.001) during the follow-up period (median interval: 180 (IQR: 42-332) days). There was no statistically differences in baseline clinical profiles or medications at discharge between the groups. However, LVEF at admission was significantly higher in the Recovery group than Non-recovery group (47±13% vs. 31±13%, p=0.014). The univariate logistic regression analysis showed that baseline LVEF was related to a recovery of LV function (odds ratio, 1.12; 95% confidence interval, 1.00-1.26). The ROC curve for a recovery of LV function revealed that the cut-off value of LVEF at admission was 42% (sensitivity: 75%, specificity: 83%, area under the curve: 0.83, Figure A ). Patients with baseline LVEF ≥42% achieved significantly higher rates of LV functional recovery after acute myocarditis than those with LVEF &lt;42% (17% vs 75%, p=0.019, Figure B ). Conclusions: Baseline LVEF could predict a normalization of LV function in patients with acute myocarditis. Close observation and TTE follow-up should be considered in such a refractory population.
Covid-19: Self-isolation is the weakest link in stopping transmission
Authors: Michael Gill
Journal: BMJ (2021)

At last the weakest link in the chain of covid-19 transmission—self-isolation—is getting the attention it deserves.1 Cevik and colleagues say that “risk of household transmission within crowded and otherwise inadequate housing intersects with financial barriers to isolation and inability to work from home.” In other words, given the practical difficulties associated with self-isolation in a confined space with shared facilities and several household members, the net effect of self-isolation across …
Non-canonical PD-1 signaling in cancer and its potential implications in clinic
Authors: Haoran Zha, Ying Jiang, Xi Wang, Jin Shang, Ning Wang, Lei Yu, Wei Zhao, Zhihua Li, Juan An, Xiaochun Zhang, Huoming Chen, Bo Zhu, Zhaoxia Li
Journal: Journal for ImmunoTherapy of Cancer (2021)

Programmed cell death 1 (PD-1)-based immunotherapy has revolutionized the treatment of various cancers. However, only a certain group of patients benefit from PD-1 blockade therapy and many patients succumb to hyperprogressive disease. Although, CD8 T cells and conventional T cells are generally considered to be the primary source of PD-1 in cancer, accumulating evidence suggests that other distinct cell types, including B cells, regulatory T cells, natural killer cells, dendritic cells, tumor-associated macrophages and cancer cells, also express PD-1. Hence, the response of patients with cancer to PD-1 blockade therapy is a cumulative effect of anti-PD-1 antibodies acting on a myriad of cell types. Although, the contribution of CD8 T cells to PD-1 blockade therapy has been well-established, recent studies also suggest the involvement of non-canonical PD-1 signaling in blockade therapy. This review discusses the role of non-canonical PD-1 signaling in distinct cell types and explores how the available knowledge can improve PD-1 blockade immunotherapy, particularly in identifying novel biomarkers and combination treatment strategies.
Upregulation of STAT1 transcription activator by an androgen agonist in prostate cancer cells affects intracellular cholesterol esterification
Authors: Jennifer Locke, Kishor Wasan, Emma Guns, Colleen Nelson, Carlos Leon
Journal: Cancer Research (2007)

LB-197  The objective of this work was to determine the effect of an androgen agonist, R1881, on intracellular cholesterol synthesis and esterification within an androgen-dependent prostate cancer cell line. We investigated the activity (using standardized radiolabeled techniques) and expression (Western Blot) of two cholesterol metabolism enzymes, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and acyl-coenzyme A:cholesterol acyltransferase (ACAT), in the LNCaP androgen-dependent prostate cancer cell model and in the PC-3 androgen-independent model for comparison. At the cellular level, when PC-3 and LNCaP cell lysates were examined for free cholesterol and cholesteryl ester content using prepared enzymatic kits, we found a decrease in free cholesterol and an increase in cholesteryl esters in LNCaP cells treated with the androgen receptor agonist R1881, compared to controls. In the PC-3 cells we did not find a change in total cholesterol or in cholesteryl esters upon R1881 treatment. HMG-CoA reductase activity in the LNCaP and PC-3 cells was increased upon androgen stimulation. Furthermore, HMG-CoA reductase protein expression in PC-3 was higher than in LNCaP cells. The increased intracellular cholesteryl ester levels found in R1881-treated LNCaP cells were not associated with an increased in vitro ACAT activity. In contrast, we found an increase in ACAT activity upon androgen stimulation in PC-3 cells. We analyzed the expression of the two ACAT isoforms, ACAT1 and ACAT2 to determine if their protein levels were affected by the R1881 treatment in both cell lines. We found that ACAT2 expression was induced in LNCaP cells treated with R1881. In the case of PC-3, ACAT1 expression was induced when the cells were treated with the androgen agonist. We investigated the mechanism of ACAT1 induction in PC-3 cells and assessed the expression of STAT1α, a transcriptional activator that modulates ACAT1 expression. We found that STAT1α expression and phosphorylation were induced by R1881 treatment in PC-3; thus it is a possible mechanism to account for increased ACAT1 expression in PC-3 cells.  Induction of STAT1α activation may lead to an increase in ACAT1 protein expression which was associated with augmented ACAT activity in PC-3 cells. Interestingly this increased ACAT activity was not associated with increased cholesteryl ester accumulation in PC-3 cells treated with R1881, suggesting that other mechanisms such as cholesterol esterases or cholesteryl ester secretion may contribute to cholesteryl ester homeostasis in prostate cells. Taken together, these findings further support the importance of cholesterol metabolism regulation within prostate cancer cells. Furthermore, they also unravel a novel role for STAT1α in prostate cancer metabolism.
Strengthening capacities and resource allocation for co-production of health research in low and middle income countries
Authors: Irene Akua Agyepong, Sue Godt, Issiaka Sombie, Charity Binka, Vicky Okine, Marie-Gloriose Ingabire
Journal: BMJ (2021)

Strengthening capacities and resource allocation for co-production of health research in low and middle income countriesIrene Agyepong and colleagues share experiences and ideas to strengthen capacity for health research co-production in low
Abstract PS7-84: Lymphovascular invasion among female patients diagnosed with breast cancer
Authors: Maharaj Singh, Santhi Konduri, Richard Rovin
Journal: Cancer Research (2021)

Abstract Background The presence of carcinoma cells in either lymphatic vessels, blood vessels or both is defined as lymphovascular invasion (LVI). The presence of LVI is associated with an increased risk of axillary lymph node and distant metastases. LVI is also characterized as one of the significant prognostic factors for the patients diagnosed with breast cancer. Objective The objective of this study is to identify predictors of LVI among female patients diagnosed with breast cancer. Method From the Commission on Cancer’s National Cancer Database from 2010 through 2016, we identified 1,220,046 female patients diagnosed with breast cancer and with non-missing value for LVI. Patient demographics, tumor characteristics and biomarkers were analyzed using descriptive statistics. Odds ratios (OR) were computed using stepwise multivariate logistics regression. All statistical analysis was done using SAS version 9.4, SAS institute, Cary, NC and for all statistical tests alpha of 0.05 was used. Results The study population included 78% non-Hispanic white (NHW), 11% non-Hispanic black, (NHB), 5% Hispanic and 6% from ‘other’ race category. The median age of the patients at the time of diagnosis was 61 years. Of the total patients, only 16 % had LVI. Significant predictors of LVI include race (Hispanic vs NHW, OR=1.03, 1.01-1.06 p=0.008; NHB vs NHW OR=0.91,0.90-0.93, p&amp;lt;0.001; ‘Other’ vs NHW OR=0.97, 0.95-1.00, p=0.018), insurance status (government vs no-insurance, OR=1.08,1.04-1.11, p&amp;lt;0.001; private vs no-insurance, OR=1.08,1.05-1.12, p&amp;lt;0.001), Charlson-Dayo Index (1 vs none, OR=1.08, 1.06 -1.09, p&amp;lt;0.001, 2 vs none, OR=1.16, 1.12 -1.20, p&amp;lt;0.001, 3 or more vs none, OR=1.16, 1.10 -1.22, p&amp;lt;0.001), primary sequence (OR=1.03,1.01-1.04, p&amp;lt;001), cancer stage (I vs 0, OR=2.99, 2.86-3.14, p &amp;lt;0.0001, II vs 0, OR=9.40,8.97-9.86 p &amp;lt;0.0001, III vs 0, OR=21.28, 20.25-22.36, p &amp;lt;0.0001, and IV vs 0, OR=15.11,14.32-15.94, p &amp;lt;0.001), ER (OR=1.02, 1.01-1.04 p=0.002), PR (OR=1.03, 1.01-1.05 p=0.002), HER2neu (equivocal vs negative OR=1.14, 1.10-1.18 p &amp;lt;0.001, positive vs negative OR=1.28, 1.26 -1.30, p &amp;lt;0.001), and 10 year increment in age at the time of diagnosis (OR=0.90, 0.89-0.90, p &amp;lt;0.001). Conclusion The predictive factors for LVI includes Hispanic race, government or private insurance, higher Charlson-Dayo scores, primary sequence, cancer stages, ER, PR and HER2neu expression. The chances LVI decreases with increasing age. These finding might provide insights for clinicians for the treatment plan for the patients. Citation Format: Maharaj Singh, Santhi Konduri, Richard Rovin. Lymphovascular invasion among female patients diagnosed with breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-84.
Abstract PD15-05: Sipa1 effects rock pathway in human breast cancer linking to HGF mediated changes in tight junction functions controlling metastasis
Authors: Chang Liu, Fiona Ruge, Lin Ye, Gregory M. Harrison, Wen G. Jiang, Tracey A. Martin
Journal: Cancer Research (2021)

Abstract Background: SIPA1 (Signal-induced proliferation-associated gene 1) is a mitogen-inducible gene encoding a GTPase-activating protein for Rap1 and Rap2 and has been suggested to be involved in metastatic progression. We have previously shown SIPA1 may regulate barrier function in breast cancer cells as part of hepatocyte growth factor-determined changes and that this may be via a number of regulatory pathways, most likely via the ROCK pathway. Our aim with this current work was to definitively identify which pathway is involved. Methods: After knockdown of SIPA1 in MDA-MB-231 cells, they were treated to a number of inhibitors to proteins involved in pathways involved in TJ barrier function (ROCK, N-WASP, ARPs, WAVEs, MAPK, ERK, PLC-gamma). Following the identification of suitable inhibitor a large scale in vivo study was carried out using a tumour model of SIPA1 knockdown versus WT control was treated with/without inhibitors and immunohistochemistry (IHC) used to assess changes in tumour growth, architecture and protein expression. We also assessed the expression of SIPA-1 in a cohort of human breast cancer tissues using IHC. Results: After knockdown of SIPA1 in MDA-MB-231 cells, we subjected cells to a number of inhibitors to proteins involved in pathways involved barrier function (ROCK, N-WASP, ARPs, WAVEs, MAPK, ERK, PLC-gamma). Analysis of behaviour showed that knockdown cells no longer responded to the ROCK inhibitor (ROCKi Y-27632, p&amp;lt;0.05, n=10). In vivo tumour samples were assessed for expression of ROCKI, expression of phospho-ROCK, and any differences when treated with ROCKi. Control tissues showed good levels of all three proteins (SIPA1, ROCKI and phosphor-ROCK). Knockdown tissues exhibited significantly lower levels of ROCK and phosphor-ROCK (p&amp;lt;0.01, n=12). In control tumours, phosphor-ROCK was increased after treatment with ROCKi; conversely, in SIPA1 knockdown tumours, phosphor-ROCK was decreased after treatment with ROCKi (p&amp;lt;0.05). In SIPA1 knockdown tissues, ROCK and phosphor-ROCK was diffuse in staining pattern when compared to the control where the staining was located at the cell membrane. Conclusion: Our results confirm our hypothesis that SIPA1 is involved in the control of TJ in breast cancer and that this is through the ROCK pathway. Moreover, these results demonstrate that this may be due to the effect that SIPA1 has on cellular ratios of ROCK to phosphor-ROCK in breast cancer. Citation Format: Chang Liu, Fiona Ruge, Lin Ye, Gregory M. Harrison, Wen G. Jiang, Tracey A. Martin. Sipa1 effects rock pathway in human breast cancer linking to HGF mediated changes in tight junction functions controlling metastasis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD15-05.
Abstract 15588: Synchrotron-based 4D-X-ray Phase Tomography of Fresh Aortic Wall of Acute Aortic Dissection
Authors: Takuro Tsukube, Koki Yokawa, Chikashi Nakai, Masato Hoshino, Naoto Yagi, Kazunori Nakagawa, Yutaka Nakashima
Journal: Circulation (2019)

Backgrounds: Mechanisms of onset of acute aortic dissection (AAD) has not been fully elucidated. Synchrotron-based X-ray phase tomography (XPCT) is a powerful tool to measure biological soft tissue...