tbuckley/cabot-search huggingface dataset:
Abstract B2-49: Coupled cellular decision-making of EMT and stemness: A bottom-up regulatory model
Authors: Mohit Kumar Jolly, Bin Huang, Mingyang Lu, Sendurai A Mani, Herbert Levine, Eshel Ben-Jacob
Journal: Cancer Research (2015)

Abstract Epithelial cells undergoing epithelial-to-mesenchymal transitions (EMT) have often been shown to behave as cancer stem cells (CSCs) but the precise molecular connection remains elusive. At the genetic level, stemness is governed by LIN28/let-7 double inhibition switch, whereas EMT/MET is controlled by miR-200/ZEB double inhibition circuit. The two switches are coupled by LIN28 being inhibited by miR-200, and ZEB being inhibited by let-7. Here, we devise a specific theoretical framework to investigate the dynamics of the LIN28/let-7 system, and show that it can operate as a three-way switch (between low, high and intermediate LIN28 levels termed the D, U and the hybrid D/U states) similar to the three-way operation of the miR-200/ZEB circuit that allows for the existence of a hybrid epithelial/mesenchymal (E/M) or partial EMT phenotype, in addition to epithelial and mesenchymal ones. We find significant correspondence between the existence of the three states of the two circuits: E-D; M-U; E/M-D/U. Incorporating the activation of OCT4 by LIN28, we find that the hybrid E/M phenotype has high likelihood (as compared to either the pure E or M states) to gain stemness. Combining the LIN28/let-7 regulation by NF-kB and c-MYC, we find that NF-kB, but not c-MYC, elevates the likelihood of E/M to gain stemness. Our results are consistent with emerging concept that cells undergoing partial EMT can gain stemness. Citation Format: Mohit Kumar Jolly, Bin Huang, Mingyang Lu, Sendurai A Mani, Herbert Levine, Eshel Ben-Jacob. Coupled cellular decision-making of EMT and stemness: A bottom-up regulatory model. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B2-49.
Abstract P5-08-19: A single-nucleotide polymorphism in the 3'-UTR region of the adipocyte fatty acid binding protein 4 gene is associated with prognosis of triple negative breast cancer
Authors: P Yuan, W Wang, C Wu, D Lin, B Xu
Journal: Cancer Research (2016)

Abstract Objective Triple negative breast cancer (TNBC) is a subtype with poor prognosis and high heterogeneity. The aim of this study was to screen single nucleotide polymorphisms (SNPs) associated with the prognosis of TNBC patients and to explore the potential mechanism. Methods We selected SNPs(MAF≥1%) located on the 3' untranslated region (3'UTR) of differentially expressed genes in breast cancer through databases (Nextbio,ensemble,NCBI,MirSNP). We investigated the possible associations between 111 SNPs and progression risk among 323 TNBC patients using two-step case-control study with discovery cohort (n=162) and validation cohort (n=161). The Benjamini Hochberg false discovery rate (FDR) method was used to assess the statistical significance after correction for multiple comparisons. Kaplan-Meier analysis was applied in order to assess the association between disease free survival (DFS) and positive SNPs, as well as Body Mass Index(BMI). We also investigated the expression of FABP4 in adipocytes adjacent to TNBC tissues (n=35) using immunohistochemistry. The integrated optical density (IOD) was measured as an approximation of FABP4 expression. Mann-Whitney U test was used in an attempt to assess the correlations among SNPs in FABP4, FABP4 expression and TNBC prognosis. Results SNPs in FABP4, KRAS and NTRK2 genes associated with the recurrence risk of TNBC throughout the discovery cohort and validation cohort, while the statistical significance was retained after multiple comparisons only for FABP4 rs1054135. The G allele of rs1057035 was associated with decreased risk of disease progression (aHR 0.14, 95%CI0.03-0.66), as well as an increased DFS (P&amp;lt;0.05). Furthermore, the expression of FABP4 was statistically significant lower in patients with rs1054135-GG genotype and those in disease-free group(P=0.0464,P=0.0061 respectively). Conclusions Our study found a lipid metabolism related gene and an important SNP in the 3'UTR of FABP4 associated with TNBC prognosis, which may aid the screening of high-risk patients with TNBC recurrence and the development of novel chemotherapeutic agents. Citation Format: Yuan P, Wang W, Wu C, Lin D, Xu B. A single-nucleotide polymorphism in the 3'-UTR region of the adipocyte fatty acid binding protein 4 gene is associated with prognosis of triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-19.
Abstract B30: Targeting EZH2 methyltransferase activity: A novel therapeutic approach to ARID1A-deficient cancer
Authors: Benjamin Bitler, Azat Garipov, Ie Ming Shih, Rugang Zhang
Journal: Cancer Research (2016)

Abstract Loss of function mutation of the epigenetic modulator ARID1A, a component of SWI/SNF chromatin remodeling complex, occurs in a number of cancers most notably ovarian. ARID1A is mutated in up to 60% and 30% of clear cell and endometrioid ovarian cancers, respectively. However, there currently is no effective therapy that targets ARID1A-deficient human cancers. Here we show ARID1A-deficient ovarian cancer cells are selectively sensitive to inhibition of EZH2's methyltransferase activity. EZH2 is the catalytic subunit of the polycomb repressor complex 2, which represses gene expression by generating tri-methylation epigenetic mark on lysine 27 of histone H3 (H3K27Me3). Utilizing a library of small molecules against epigenetic targets, we identified an EZH2 small molecule inhibitor that selectively inhibited the growth of ARID1A-deficient ovarian cancer cells, while exhibiting no effects in ARID1A wild-type cells. Genome-wide gene expression profile revealed that there is significant overlap of genes altered by ARID1A restoration and EZH2 methyltransferase inhibition. Specifically, the tumor suppressor and inhibitor of PI3K/AKT signaling, PIK3IP1, is regulated by both ARID1A and EZH2. Chromatin immunoprecipitation assays confirmed the occupancy of ARID1A and EZH2 at the PIK3IP1 promoter. In an intraperitoneal (IP) xenograft mouse model, EZH2 inhibitor GSK126 treatment resulted in a significant decrease in the number of IP tumor nodules. Moreover, in an independent orthotopic intra-bursal xenograft model using ARID1A wildtype and deficient cells, the EZH2 inhibitor GSK126 only suppressed the growth of ARID1A-deficient tumors. Notably, the observed effects correlated with a decrease in expression of H3K27Me3, pAKT and Ki67, a cell proliferation marker, and an increase in PIK3IP1. These data indicate loss of ARID1A and gain of EZH2 could act in epigenetic concert to promote cancer phenotypes. Taken together, these findings imply that inhibition of the methyltransferase EZH2 represents a novel therapeutic strategy for ARID1A-deficient cancers. Citation Format: Benjamin Bitler, Azat Garipov, Ie Ming Shih, Rugang Zhang. Targeting EZH2 methyltransferase activity: A novel therapeutic approach to ARID1A-deficient cancer. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr B30.
Outbreak of imported trichinellosis in Verona, Italy, January 2008
Authors: A Angheben, M Mascarello, G Zavarise, F Gobbi, G Monteiro, S Marocco, M Anselmi, A Azzini, E Concia, A Rossanese, Z Bisoffi
Journal: Eurosurveillance (2008)

We describe an outbreak of trichinellosis in Verona, Italy, in early 2008 that was imported from Romania.
Abstract A08: Telomerase inhibition brings metabolic compromises in glioblastoma multiforme (GBM)
Authors: Fahim Ahmad, Ellora Sen
Journal: Cancer Research (2016)

Abstract Introduction: A defining characteristic of cancer cells is their ability to circumvent multiple regulatory mechanisms that normally restrict cell proliferation. Understanding the links between aberrant metabolic adaptation and prosurvival responses in glioma cells is crucial towards the development of new anti-glioma therapies. Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the telomerase holoenzyme. The telomere maintenance or telomerase activity is mainly driven by hTERT and hTERC. A large number of reports suggest an ever increasing role of telomere maintenance in cancer progression. We sought to evaluate its involvement in the regulation of metabolic status in these cells. Methods: Human glioma cell lines A172 and U87MG Cells were grown in DMEM supplemented with 10% FBS. On attaining semi confluence, cells were switched to SFM (serum free media) for 4 hrs and further treated with Telomerase inhibitor for 24hrs. Glioma cell lines were transiently transfected with lipofectamine 2000 and lipofectamine RNAi max reagents. Cells were harvested 48hrs post transfection. Heterotropic glioma xenografts were generated upon injecting U87MG cells subcutaneously in flank region of nude mice. After 20 days of injection, prominent tumor volume was visible. Thereafter, mice were grouped and administered either with PBS or Telomerase inhibitor for 20 days on every alternate day. Mice were sacrificed and tissues were processed for subsequent experiments. Histochemically identified TERT mutant and wild type human glioma samples were also used to unravel the ongoing signaling cascades. Results: Inhibition of telomerase resulted in metabolic compromises. TERT was found to regulate the expression of an important transcription factor responsibe for maintenance of metabolic and antioxidant proteins. The expression of this transcription factor was concomitant with altered metabolic profile as characterized by decreased pentose phosphate pathway. TERT regulated expression of PPP genes seemed to have its effect on prosurvival and antioxidant molecules. Conclusions: hTERT plays a key role in survival responses by modulating the metabolic status of glioma cells both in vitro and in vivo. By switching the signals under the control of a metabolic sensor (transcription factor) that modifies energy status to govern anti proliferative environment, hTERT regulates both survival responses and energy status. Citation Format: Fahim Ahmad, Ellora Sen. Telomerase inhibition brings metabolic compromises in glioblastoma multiforme (GBM). [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A08.
Psychiatric consultation in the management of patient ambivalence interfering with the doctor-patient relationship
Authors: K Kris
Journal: American Journal of Psychiatry (1981)

The author describes states of patient ambivalence as a regressive response to illness that may interfere with the patient-staff alliance. She provides three illustrations of such ambivalence and tells how they were handled by psychiatric consultation in an obstetrical hospital. She describes the characteristics of the difficulties caused by patient ambivalence in the doctor-patient relationship and makes a number of suggestions for the management of ambivalence by the psychiatric consultant.
Interleukin-15 Triggers Activation and Growth of the CD8 T-Cell Pool in Extravascular Tissues of Patients With Acquired Immunodeficiency Syndrome
Authors: Carlo Agostini, Livio Trentin, Rosaria Sancetta, Monica Facco, Cristina Tassinari, Andrea Cerutti, Michela Bortolin, Antonella Milani, Marta Siviero, Renato Zambello, Gianpietro Semenzato
Journal: Blood (1997)
Progression of illness in the differential diagnosis of primary dementia
Authors: G S Zubenko
Journal: American Journal of Psychiatry (1990)

The diagnostic utility of determinations of insidious or stepwise progression of illness was examined in 124 geriatric inpatients with primary dementia. Such determinations failed to distinguish patients with primary degenerative dementia of the Alzheimer type from those with multi-infarct dementia. Episodic behavioral complications, especially depression and delusions, in the patients with primary degenerative dementia were associated with stepwise progression. Determinations of stepwise progression were made in only six (15%) of the 40 demented patients with at least two cerebral infarctions, a finding inconsistent with current diagnostic criteria for multi-infarct dementia.
Abstract P2-08-14: Validation of gene expression profiling in prediction of locoregional recurrence for breast cancer patients after surgery
Authors: H-CS Cheng, C-F Horng, T-T Huang, M-H Tsou, L-S Shih, B-L Yu, Y-C Tsai, C-M Chen
Journal: Cancer Research (2016)

Abstract Purpose We have identified 34 genes of interest that can distinguish post-mastectomy cancer patients into high- and low-risk of locoregional recurrence (LRR) in 2006. In this study, we validate the performance of 18 of 34 genes in prediction of LRR after mastectomy and breast conserving surgery (BCS). Materials and methods A total of 124 breast cancer patients who underwent mastectomy from 2005 to 2012 and had DNA microarray study on the primary tumor tissues were chosen for this study. Eligible patients should have no post-mastectomy radiotherapy (PMRT) with a minimum of 2-year follow-up. Among the 34 genes in previous report, only 30 genes could be found in Affymetrix U95 to U133 Plus2.0 array. Eighteen of 30 genes (18-Gene classifier) were used to distinguish low-risk and high-risk patients. Patients with 18-Gene score 31 or more were defined as high-risk and score less than 31 defined as low-risk group. We then examined the performance of the 18-Gene classifier in breast conserving patients (n=87) who usually had adjuvant radiotherapy (94%) and were treated in the same study periods. Results The overall accuracy of the prediction of LRR is 87% (sensitivity 91% and specificity 87%). By the 18-Gene classifier, the 5-year LRR rate in high-risk group was 42%, and in low-risk group &amp;lt;1% (p &amp;lt; 0.0001). LRR and 18-gene score in non-PMRT patients18-Gene scoreNo LRR #LRR #5-year LR control probabilityScore &amp;lt;31971100%Score &amp;gt;= 31151157.7% 11212 LRR: Locoregional recurrence Multivariate analysis of mastectomy patients revealed that 18-Gene score is the independent prognostic factor that predicts the likelihood of LRR regardless of nodal status and breast cancer subtype. The predictive ability of LRR by the 18-Gene classifier in BCS patients is independent from adjuvant radiotherapy, and is consistent with the performance in mastectomy patients. Multivariate analysis in BCS patientsRisk factorPatient #LRR #LRR rateUnivariate analysisMultivariate analysisLVI Absent/focal7345.5% Prominent14321.4%4.3(1.0,19.3)5.1*(1.1,23.1)18-Gene score Low risk6623.0% High risk21523.8%9.4*(1.8,48.4)10.4*(2.0,54.2)Adjuvant R/T No5240%10.3*(2.0,53.9) Yes8256.1% LVI: lymphovascular invasion; R/T: radiotherapy; *p&amp;lt;0.05 Discussion This 18-Gene classifier is capable of identifying high-risk patients of LRR after mastectomy and breast conserving surgery. Citation Format: Cheng H-CS, Horng C-F, Huang T-T, Tsou M-H, Shih L-S, Yu B-L, Tsai Y-C, Chen C-M. Validation of gene expression profiling in prediction of locoregional recurrence for breast cancer patients after surgery. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-14.
Thymectomy in Myasthenia Gravis
Authors: L Noyez, T Lerut, J A Gruwez, J A Bulcke
Journal: BMJ (1949)

Myasthenia gravis is an autoimmundisease characterized by muscle fatigability due to a reduction in available acetylcholinereceptors at neuromuscular junction. Although the role of the thymus in the pathophysiology remains obscure, the results of thymectomy are out of discussion. However, controversy continues concerning the indications for thymectomy. In a period of six years and a half, 24 patients underwent a thymectomy. 22 of the patients benefited from the procedure. Their was no relation with sex, age, and severity of the disease; but how sooner we operate, how greater the changes for a total remission. With this results we propose thymectomy as essential in the treatment of myasthenia gravis. We found no relationship between anatomopathological results and these of the thymectomy. But we can confirm that a reduction in the acetylcholine antibodies titer is not essential for clinical benefit.
Controlling Bone Graft Substitute Microstructure to Improve Bone Augmentation
Authors: Zeeshan Sheikh, Justin Drager, Yu Ling Zhang, Mohamed‐Nur Abdallah, Faleh Tamimi, Jake Barralet
Journal: Advanced Healthcare Materials (2016)

Vertical bone augmentation procedures are frequently carried out to allow successful placement of dental implants in otherwise atrophic ridges and represent one of the most common bone grafting procedures currently performed. Onlay autografting is one of the most prevalent and predictable techniques to achieve this; however, there are several well documented complications and drawbacks associated with it and synthetic alternatives are being sought. Monetite is a bioresorbable dicalcium phosphate with osteoconductive and osteoinductive potential that has been previously investigated for onlay bone grafting and it is routinely made by autoclaving brushite to simultaneously sterilize and phase convert. In this study, monetite disc‐shaped grafts are produced by both wet and dry heating methods which alter their physical properties such as porosity, surface area, and mechanical strength. Histological observations after 12 weeks of onlay grafting on rabbit calvaria reveal higher bone volume (38%) in autoclaved monetite grafts in comparison with the dry heated monetite grafts (26%). The vertical bone height gained is similar for both the types of monetite grafts (up to 3.2 mm). However, it is observed that the augmented bone height is greater in the lateral than the medial areas of both types of monetite grafts. It is also noted that the higher porosity of autoclaved monetite grafts increases the bioresorbability, whereas the dry heated monetite grafts having lower porosity but higher surface area resorb to a significantly lesser extent. This study provides information regarding two types of monetite onlay grafts prepared with different physical properties that can be further investigated for clinical vertical bone augmentation applications.
Effects of pill-giving on maintenance of placebo response in patients with chronic mild depression
Authors: J G Rabkin, P J McGrath, F M Quitkin, E Tricamo, J W Stewart, D F Klein
Journal: American Journal of Psychiatry (1990)

Fifty outpatients with mild, chronic, mood-reactive depression whose mood improved markedly after a 10-day single-blind placebo trial were randomly assigned in a double-blind design either to have their placebo medication discontinued or to have it maintained for an additional 6 weeks. Half of the patients in each condition relapsed within 6 weeks, indicating that pill-taking itself does not influence maintenance of placebo response. Placebo response was more likely to be maintained in patients who were currently married. At the end of 3 months, the overall relapse rate was 58%. The authors raise questions about the utility of the initial 10-day placebo washout in antidepressant clinical trials, and they discuss limits on the generalizability of their findings.
Abstract ES4-1: Longitudinal strategies in ER+ disease
Authors: M Dickler
Journal: Cancer Research (2016)

Abstract Endocrine therapy is a relatively well-tolerated treatment for hormone receptor-positive (HR+) breast cancer. This therapy can be offered as first-line treatment before initiation of chemotherapy in patients with manageable symptoms from their disease and no evidence of clinically significant compromise of visceral organ function. Targeting the estrogen receptor pathway with agents such as the aromatase inhibitors, tamoxifen and fulvestrant can provide effective therapy with a durable response to treatment for some patients. This presentation will review clinical trial data to guide choice of endocrine therapy and the sequential use of these agents in patients with endocrine-responsive disease. Within HR+ breast cancer, there is molecular diversity that can influence responsiveness to endocrine therapy. In addition, recent insight into the complex interactions between the estrogen receptor and cell cycle survival and/or growth factor signalling pathways have uncovered potential mechanisms of endocrine therapy resistance in HR+ breast cancer. This improved understanding has led to new options for treatment. We will review the clinical trial evidence that supports the addition of a cell cycle inhibitor, palbociclib, to first-line letrozole and second-line fulvestrant. We will also review evidence supporting the combination of an mTOR inhibitor, everolimus, to second- or third-line exemestane. These targeted agents increase progression-free survival when added to endocrine therapy, however at the present time, there is no benefit in overall survival. With this limitation in mind, we will review the side effects of these agents, weigh the toxicity and potential benefits, and examine if patient and/or tumor-based factors may help to determine which patients are best suited for these agents. Lastly, we will discuss the subset of patients with bone-only HR+ disease, and the complexities of assessing imaging and their response to therapy. Citation Format: Dickler M. Longitudinal strategies in ER+ disease. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr ES4-1.
Comment on Sjöholm et al. Weight Change–Adjusted Effects of Gastric Bypass Surgery on Glucose Metabolism: 2- and 10-Year Results From the Swedish Obese Subjects (SOS) Study. Diabetes Care 2016;39:625–631
Authors: Konstantinos Spaniolas, Walter J. Pories
Journal: Diabetes Care (2016)

We read with interest the article by Sjoholm et al. (1) in Diabetes Care on the effect of Roux-en-Y gastric bypass (RYGB) on glucose metabolism 2 and 10 years following surgery. The authors used data from the Swedish Obese Subjects (SOS) study and compared fasting glucose, insulin, and HOMA of insulin resistance (HOMA-IR) in patients who underwent gastric banding (GB), RYGB, or vertical banded gastroplasty (VBG). To evaluate for procedure-specific effects of RYGB, they compared groups on the basis of percent total body weight loss and concluded that weight loss is more important than procedure type for long-term improvements in glucose metabolism. The authors hypothesized that short-term and long-term improvements in glucose metabolism are different. We fully agree with this concept. In our studies (2), early improvements in glucose metabolism after RYGB occurred before any change …