tbuckley/cabot-search huggingface dataset:
Lower Abnormal Fecal Immunochemical Test Cut-Off Values Improve Detection of Colorectal Cancer in System-Level Screens
Authors: Emily Berry, Stacie Miller, Mark Koch, Bijal Balasubramanian, Keith Argenbright, Samir Gupta
Journal: Clinical Gastroenterology and Hepatology (2019)

Noninvasive tests used in colorectal cancer screening, such as the fecal immunochemical test (FIT), are more acceptable but detect neoplasias with lower levels of sensitivity than colonoscopy. We investigated whether lowering the cut-off concentration of hemoglobin for designation as an abnormal FIT result increased the detection of advanced neoplasia in a mailed outreach program.
Upregulation of Scavenger Receptor B1 Is Required for Steroidogenic and Nonsteroidogenic Cholesterol Metabolism in Prostate Cancer
Authors: Jacob A. Gordon, Jake W. Noble, Ankur Midha, Fatemeh Derakhshan, Gang Wang, Hans H. Adomat, Emma S. Tomlinson Guns, Yen-Yi Lin, Shancheng Ren, Collin C. Collins, Peter S. Nelson, Colm Morrissey, Kishor M. Wasan, Michael E. Cox
Journal: Cancer Research (2019)

Aberrant cholesterol metabolism is increasingly appreciated to be essential for prostate cancer initiation and progression. Transcript expression of the high-density lipoprotein-cholesterol receptor scavenger receptor B1 (SR-B1) is elevated in primary prostate cancer. Hypothesizing that SR-B1 expression may help facilitate malignant transformation, we document increased SR-B1 protein and transcript expression in prostate cancer relative to normal prostate epithelium that persists in lethal castration-resistant prostate cancer (CRPC) metastasis. As intratumoral steroid synthesis from the precursor cholesterol can drive androgen receptor (AR) pathway activity in CRPC, we screened androgenic benign and cancer cell lines for sensitivity to SR-B1 antagonism. Benign cells were insensitive to SR-B1 antagonism, and cancer line sensitivity inversely correlated with expression levels of full-length and splice variant AR. In androgen-responsive CRPC cell model C4-2, SR-B1 antagonism suppressed cholesterol uptake,
Abstract P6-21-02: Withdrawn
Authors: C Minichsdorfer, E Bergen, GG Steger, G Pfeiler, S Frantal, R Greil, H Fohler, D Egle, M Balic, F Fitzal, V Wette, R Exner, RA Bartsch, M Gnant
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Minichsdorfer C, Bergen E, Steger GG, Pfeiler G, Frantal S, Greil R, Fohler H, Egle D, Balic M, Fitzal F, Wette V, Exner R, Bartsch RA, Gnant M. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-21-02.
First-in-Human Phase I Study of the Activin A Inhibitor, STM 434, in Patients with Granulosa Cell Ovarian Cancer and Other Advanced Solid Tumors
Authors: Jessica J. Tao, Nicholas A. Cangemi, Vicky Makker, Karen A. Cadoo, Joyce F. Liu, Drew W. Rasco, Willis H. Navarro, Christopher M. Haqq, David M. Hyman
Journal: Clinical Cancer Research (2019)

Abstract Purpose: STM 434 is a soluble receptor ligand trap targeting activin A, a protein in the TGFβ family that plays important roles in growth, differentiation, and cancer cachexia. This study evaluated the safety, antitumor activity, and metabolic effects of STM 434 in a first-in-human, multicenter, phase I clinical trial (NCT02262455). Patients and Methods: Patients with advanced solid tumors were enrolled in 8 dose cohorts ranging from 0.25 mg/kg every 4 weeks to 8 mg/kg every 2 weeks via a 3 + 3 dose-escalation design. The primary endpoint was maximum tolerated dose (MTD). Secondary endpoints included safety, pharmacokinetics, and response. As activin A is implicated in metabolism and muscle function, changes in key metabolic parameters, including lean body mass and 6-minute walk test, were serially measured. Results: Thirty-two patients were treated on study. The most common treatment-related adverse events were fatigue (41%) and mucocutaneous bleeding complications including epistaxis (34%) and gingival bleeding (22%), likely related to off-target inhibition of bone morphogenetic protein 9 (BMP9). STM 434 treatment resulted in the expected follicle-stimulating hormone level decreases in most patients and in metabolic parameter changes, including an increase in total lean body mass and 6-minute walk test distance. No responses were observed in the 30 evaluable patients, but the stable disease rate in patients with granulosa cell ovarian cancer was 10 of 12 (80%). Conclusions: Although no direct antitumor efficacy was documented, potentially clinically meaningful dose-related metabolic effects, including treatment of cancer cachexia, were observed that support further exploration of activin A inhibitors that limit BMP9 blockade. See related commentary by Bonilla and Oza, p. 5432
Durvalumab in Combination with Olaparib in Patients with Relapsed SCLC: Results from a Phase II Study
Authors: Anish Thomas, Rasa Vilimas, Christopher Trindade, Rebecca Erwin-Cohen, Nitin Roper, Liqiang Xi, Venkatesh Krishnasamy, Elliot Levy, Andy Mammen, Samantha Nichols, Yuanbin Chen, Vamsidhar Velcheti, Faye Yin, Eva Szabo, Yves Pommier, Seth M. Steinberg, Jane B. Trepel, Mark Raffeld, Howard A. Young, Javed Khan, Stephen Hewitt, Jung-Min Lee
Journal: Journal of Thoracic Oncology (2019)
Abstract P4-06-04: Targeting neo-epitopes from <i>PIK3CA</i> and <i>p53</i> mutations for immunotherapy of breast cancer
Authors: M Chen, P Yuvaraj, AA Sharma, P Narang, MA Wilson Sayres, KS Anderson
Journal: Cancer Research (2019)

Abstract Introduction: Preclinical data suggests that priming T cell immunity to mutated or overexpressed proteins can induce tumor rejection, and may potentiate the effects of checkpoint blockade. PIK3CA and p53 are the most commonly mutated genes in breast cancer, and are enriched in high-grade and metastatic tumors. Here, we evaluated the immunogenicity of neo-epitopes derived from common PIK3CA and p53 mutations. Methods: We applied a custom informatics pipeline, EpitopeHunter, to predict neo-epitopes (8-11mers) from twelve PIK3CA and ten p53 mutations restricted to thirty-nine MHC class I alleles. We selected high affinity neo-epitopes (IEDB score &amp;lt; 500) with predicted poor binding of the matched wild type epitope. We used the predicted peptides to stimulate PBMC from healthy donors in vitro, and measured T cell immunity by interferon-γ ELISPOT. We compared the T cell specificity of mutant vs wild type epitopes. A positive response to an epitope was defined as a response that met both of the following criteria: 1) net number of spots (after subtracting background) was &amp;gt;5 spots/50,000 cells and 2) net number of spots exceeded the background spots plus two SDs. Results: In total, 1,824 PIK3CA and 1,520 p53 derived peptide sequences were generated. Of these, 42 PIK3CA (2%) and 45 p53 (3%) peptides were predicted to bind to the HLA class I molecules included in our study. Over 90% of the neo-epitopes were 9- and 10-mers, and the predicted neo-epitopes varied across mutations (range 2-10 per mutation). PIK3CAH1047L and p53R248W had the highest number of potential binding neo-epitopes (n=10 each). We successfully generated T cell lines specific for A*0201 PIK3CAH1047L, A*1101 PIK3CAH1047L, A*1101 PIK3CAE542K and A*0201 p53R248W. Conclusions: Common mutations of PIK3CA and p53 can lead to the generation of potential HLA class I restricted neo-epitopes. We identified four immunogenic neo-epitopes, which may serve as candidates for targeted immunotherapy in breast cancer. Citation Format: Chen M, Yuvaraj P, Sharma AA, Narang P, Wilson Sayres MA, Anderson KS. Targeting neo-epitopes from PIK3CA and p53 mutations for immunotherapy of breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-04.
Complaints by students about UK universities rise for seventh year in row
Authors: Eva Dumann
Journal: BMJ (2013)

The number of complaints by students rose to a record level in 2012, says the annual report of the Office of the Independent Adjudicator (OIA). This is the seventh consecutive year in which numbers of complaints have risen.

The OIA is an independent body reviewing student complaints from universities in England and Wales. It is often a late or final port of call in cases not resolved by internal processes of the university concerned.

The number of complaints received by the …
Abstract 5041: Characterization of the <i>miR-125b1</i> promoter in breast cancer cell lines
Authors: Fernanda Cisneros Soberanis, Ernesto Soto Reyes, Clementina Castro, Felix Recillas Targa, Luis A. Herrera
Journal: Cancer Research (2012)

Abstract In cancer cells, transcriptional gene silencing has been associated with genetic and epigenetic defects. The disruption of DNA methylation patterns and covalent histone marks has been associated with cancer development. Until recently, microRNA (miRNA) gene silencing was not well understood. In particular, miR-125b1 has been suggested to be a miRNA with tumor suppressor activity, and it has been shown to be deregulated in various human cancers. In this study, we characterized the promoter of the miR-125b1 and the modifications associated with gene silencing. We studied in silico the miR-125b1 locus to delimit the promoter region and then, we characterized the promoter activity by the luciferase assay, cloning a fragment in the 5′ extreme close to the transcriptional start site of the miR-125b1 gene. We found that this sequence has promoter activity and it is unidirectional. Subsequently, we analyzed the DNA methylation status in the CpG island promoter and found that it was methylated in breast cancer cell lines compared with a non-transformed breast cell line. To determine the effect of DNA methylation in the CpG island of miR-125b1 on the expression of this gene, we performed a qRT-PCR assay. We observed a significant reduction on the expression of miR-125b1 in cancer cells lines in comparison with a non-transformed cell line, suggesting that DNA methylation at the CpG island might reduce the expression of miR-125b1. Our data suggest that the fragment in the 5′ extreme close to the transcriptional start site of the miR-125b1 gene is a functional and unidirectional promoter. Also, the CpG island in this region is methylated in breast cancer cell lines and this methylation is associated with the silencing of the miR-125b1 gene. This work was supported by the Consejo Nacional de Ciencia y Tecnología (CONACyT: 83959) and the Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica of the Universidad Nacional Autónoma de México (PAPIIT, IN213311). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5041. doi:1538-7445.AM2012-5041
Therapeutic Effects of a Novel Fusion of ALT-803, an IL-15 Superagonist, with 4 Single-Chains of Anti-CD20 Antibody (2B8T2M) in Combination with Expanded Natural Killer Cells Against Rituximab Sensitive and Resistant Burkitt Lymphoma (BL)
Authors: Yaya Chu, Nang Kham Su, Sarah Alter, Emily K Jeng, Peter R Rhode, Matthew J. Barth, Dean Anthony Lee, Hing C Wong, Mitchell S. Cairo
Journal: Blood (2017)
A Diminutive Invasive Sigmoid Colon Tumor Observed by Endocytoscopy
Authors: Taishi Okumura, Shin-ei Kudo, Katsuro Ichimasa
Journal: Clinical Gastroenterology and Hepatology (2019)

A 69-year-old man was referred for colonoscopy because of a positive fecal occult blood test result. He had no history of any cancer and no family history of colorectal cancer. The colonoscopy showed a 5-mm reddish polyp surrounded by a white spot in the sigmoid colon (Figure A). Chromoendoscopy with indigo carmine revealed that the lesion had a central depression (Figure B). Endocytoscopy (CF-H290ECI; Olympus, Tokyo, Japan), which is a next-generation endoscopic technology that enables cellular imaging at ×520 magnification, was performed. On endocytoscopy, unclear gland formation and agglomeration of distorted nuclei strongly stained with methylene blue were visible, which implied exposure of cancer cells to the surface of the lesion (Figure C). On the basis of these endoscopic findings, laparoscopic sigmoid colectomy, rather than endoscopic resection, was performed because the lesion was suspected to be submucosal invasive cancer. Histopathologic findings revealed well-differentiated tubular adenocarcinoma deeply invading the submucosal layer (Figure D). In addition, vascular invasion was also positive. There has not been any evidence of recurrence on follow-up colonoscopy. Diminutive colon cancer invading the submucosal layer is rare, but ultrahigh magnification endoscopy could be useful for the prediction of the pathology.
Racial Disparities in Mortality Associated with Systemic Lupus Erythematosus — Fulton and DeKalb Counties, Georgia, 2002–2016
Authors: S. Sam Lim, Charles G. Helmick, Gaobin Bao, Jennifer Hootman, Rana Bayakly, Caroline Gordon, Cristina Drenkard
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Following systemic lupus erythematosus (SLE) patients carefully defined in a population-based registry, standardized mortality ratios were two to four times higher in persons with SLE than in the general population.
Abstract P3-10-27: Profiling of metastatic carcinomas to the breast for the biomarkers of immuno-oncology therapy
Authors: Z Gatalica, W Senarathne, S Vranic, BA Pockaj
Journal: Cancer Research (2019)

Abstract Introduction: Breast metastases from non-mammary carcinomas are very rare and the molecular characteristics of these metastases have not been studied. Due to the uniqueness of this type of metastases, we evaluated whether there was any molecular or immunologic similarities among the patients with metastases to the breast. Patients and Methods: Fifty-one patients with metastatic carcinomas to the breast (49 female and 2 male) were identified in the files of Caris Life Sciences (Phoenix, AZ). Average age at presentation was 57 years (range, 20-90 years). Immunohistochemistry for PD-L1 was performed using SP142 (Ventana) or 22c3 (DAKO) antibodies; 592 genes sequencing (n=47), DNA microsatellite instability (MSI) (n=6) and total mutational burden (TMB) (n=14) were obtained from a next generation sequencing platform (Illumina). Results: Three most common primary sites were lung (19, 37%), ovary (15, 29%) and fallopian tubes/peritoneum (7, 14%). Ten metastases (20%) demonstrated neuroendocrine differentiation. When 1% cutoff was applied, tumor cells PD-L1 expression was detected in 10 cases (20%), and immune cells expression of PD-L1 in 19 patients (37%). Three cases (6%) had PD-L1 staining in both cancer and infiltrating immune cells. 50% of the cases exhibited mutations in TP53 gene, while other mutated genes followed the pathways typically seen in their primary sites (e.g. VHL in renal carcinomas, BRCA1 in fallopian tube carcinoma). Total mutational burden was high (≥10 mutations/Mb) in five out of 14 successfully analyzed cases (36%) and no case (0%) exhibited high microsatellite instability. Interestingly, estrogen receptor status was positive in 13/49 patients (26.5%) including 12 adenocarcinomas originating from ovary, Fallopian tube or peritoneum and one duodenal neuroendocrine. No tumor was HER2 positive. Conclusions: Metastases to the breast proved to be heterogeneous but there were molecular, endocrine and immunologic findings that yielded information that could be used to make therapeutic decisions which including the use of new immunotherapeutic strategies. Citation Format: Gatalica Z, Senarathne W, Vranic S, Pockaj BA. Profiling of metastatic carcinomas to the breast for the biomarkers of immuno-oncology therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-27.
Abstract P2-08-56: Effects of young age on prognosis in patients with node-negative tumors 2 cm or smaller breast cancer
Authors: W Zhong, L Tan, N You, Y Wang, G Liang, Z Liu, Y Ling, Z Tian, C Gong
Journal: Cancer Research (2019)

Abstract Background It is still controversial to consider age as a prognostic factor into the treatment strategy of patients with T1N0M0 breast cancer. Aim The main purpose of this study was to evaluate the effect of age on recurrence risk in patients diagnosed with T1N0M0 breast cancer as well as compare the prognosis of young aged patients(YA,≤40 years old) to non-young aged patients(non-YA,&amp;gt;40 years old) by using a propensity score matching(PSM) analysis. Methods 365 patients with T1N0M0 breast cancer diagnosed between 2003 and 2016 who received surgery in Sun Yat-sen Memorial Hospital Breast Cancer Center were included.The recurrence free survival (RFS) and risk factors for recurrence were identified by using Kaplan-Meier method and Cox proportional hazards models. PSM was then used to reduce the confounding effect of known risk factors on prognosis and then to compare 5-year RFS rates in patients between two age groups. Results After a median follow up of 79 months, 54 patients developed recurrences and 5-year RFS was 87.6%. YA patients had lower RFS estimates (80.6%), compared to patients diagnosed in a later age (89.1% if older than 40-years old; P = 0.049). YA patients tended to have Her-2 positive, TNBC tumors, higher rate of Ki-67 expression and nuclear grade tumor. At multivariate analysis, Her-2 positive (HR 2.115; 95% CI 1.103-4.055, p=0.024) and TNBC (HR 2.963; 95% CI 1.485-5.914, p=0.002) resulted independent prognostic factors of patient with T1N0M0 breast cancer. In the subgroup analysis, we found significant poor RFS for YA patients with Her-2 positive breast cancer compared to the older counterparts(p=0.006) and YA patients were associated with significantly higher rates of the locoregional recurrence rather than metastasis(p=0.004), especially in first 5 years after diagnosis. After PSM, the baseline level and treatment status including tumor size, grade, HR status, Her-2 status, Ki67 expression breast surgery type and systemic adjuvant treatment(AST) of patients in the two age groups tended to be equal. As result, we found significant difference in the 5-year RFS between two age groups(p=0.008). Conclusion Based on equal treatment condition, young age at presentation conferred a worse prognosis in patients with T1N0M0 breast cancer is independent on other pathological features. Citation Format: Zhong W, Tan L, You N, Wang Y, Liang G, Liu Z, Ling Y, Tian Z, Gong C. Effects of young age on prognosis in patients with node-negative tumors 2 cm or smaller breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-56.
The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content
Authors: Yftach Gepner, Ilan Shelef, Oded Komy, Noa Cohen, Dan Schwarzfuchs, Nitzan Bril, Michal Rein, Dana Serfaty, Shira Kenigsbuch, Hila Zelicha, Anat Yaskolka Meir, Lilac Tene, Avital Bilitzky, Gal Tsaban, Yoash Chassidim, Benjamin Sarusy, Uta Ceglarek, Joachim Thiery, Michael Stumvoll, Matthias Blüher, Meir J. Stampfer, Assaf Rudich, Iris Shai
Journal: Journal of Hepatology (2019)

It is unclear if a reduction in hepatic fat content (HFC) is a major mediator of the cardiometabolic benefit of lifestyle intervention, and whether it has prognostic significance beyond the loss of visceral adipose tissue (VAT). In the present sub-study, we hypothesized that HFC loss in response to dietary interventions induces specific beneficial effects independently of VAT changes.In an 18-month weight-loss trial, 278 participants with abdominal obesity/dyslipidemia were randomized to low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC + 28 g walnuts/day) diets with/without moderate physical activity. HFC and abdominal fat-depots were measured using magnetic resonance imaging at baseline, after 6 (sub-study, n = 158) and 18 months.Of 278 participants (mean HFC 10.2% [range: 0.01%-50.4%]), the retention rate was 86.3%. The %HFC substantially decreased after 6 months (-6.6% absolute units [-41% relatively]) and 18 months (-4.0% absolute units [-29% relatively]; p <0.001 vs. baseline). Reductions of HFC were associated with decreases in VAT beyond weight loss. After controlling for VAT loss, decreased %HFC remained independently associated with reductions in serum gamma glutamyltransferase and alanine aminotransferase, circulating chemerin, and glycated hemoglobin (p <0.05). While the reduction in HFC was similar between physical activity groups, MED/LC induced a greater %HFC decrease (p = 0.036) and greater improvements in cardiometabolic risk parameters (p <0.05) than the LF diet, even after controlling for VAT changes. Yet, the greater improvements in cardiometabolic risk parameters induced by MED/LC were all markedly attenuated when controlling for HFC changes.%HFC is substantially reduced by diet-induced moderate weight loss and is more effectively reduced by the MED/LC diet than the LF diet, independently of VAT changes. The beneficial effects of the MED/LC diet on specific cardiometabolic parameters appear to be mediated more by decreases in %HFC than VAT loss.High hepatic fat content is associated with metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. In the CENTRAL 18-month intervention trial, a Mediterranean/low-carbohydrate diet induced a greater decrease in hepatic fat content than a low-fat diet, conferring beneficial health effects that were beyond the favorable effects of visceral fat loss. ClinicalTrials.gov Identifier: NCT01530724.
The Preventive Effect of Parotid Gland Massage on Salivary Gland Dysfunction During High-Dose Radioactive Iodine Therapy for Differentiated Thyroid Cancer
Authors: Seung Hyun Son, Chang-Hee Lee, Ji-Hoon Jung, Do-Hoon Kim, Chae Moon Hong, Ju Hye Jeong, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, Byeong-Cheol Ahn
Journal: Clinical Nuclear Medicine (2019)

To evaluate the preventive effect of parotid gland (PG) massage for PG damage during the I therapy, we prospectively investigated the serum amylase value and salivary gland scintigraphy (SGS) after I therapy.One hundred patients with thyroidectomized differentiated thyroid cancer who underwent high-dose I therapy were enrolled in the clinical trial and randomized into 2 groups (PG massage group and nonmassage group). The serum amylase value was obtained before and 24 hours after I therapy, and the SGSs were also taken just before and at 8 months after the I therapy. Change in serum amylase value and SGS was compared between PG massage and nonmassage groups.The difference value of serum amylase was significantly lower in PG massage group than in nonmassage group (P = 0.0052). Worsening of PG function on SGS was observed in 43 (45.3%) of the 95 patients. The incidence rate of PG abnormality on F/U SGS was significantly lower in PG massage group than in nonmassage group (odds ratio, 0.3704; P = 0.0195). In the multiple regression analysis, PG massage significantly affected the abnormality on the 8-month F/U SGS (rpartial = -0.2741, P = 0.0090) after adjusting for clinical variables (age, sex, TNM stage, TSH preparation methods for the I therapy, and I dose).PG gland massage significantly reduced the incidence rates of salivary gland dysfunction on the 8-month F/U SGS and the level of the serological marker of salivary gland destruction after I therapy. Therefore, PG gland massage could alleviate salivary gland damage related to I therapy.