tbuckley/cabot-search huggingface dataset:
Abstract P4-03-01: Vacuum assisted core-needle biopsy after neoadjuvant therapy in breast cancer to predict the status of pathologic response
Authors: Regina Große, Antonia Lebioda, Jana Saegenschnitter, Tin Dao Nguyen, Holger Zentgraf, Joerg Buchmann, Christine Fathke, Susanne Steer, Christoph Thomssen
Journal: Cancer Research (2020)

Abstract Introduction: Neoadjuvant breast cancer therapy trials have documented impressive rates of pathologic complete response (pCR) of up to 70% and above, depending on grade, hormone receptor and HER2 receptor status and type of therapy. The purpose of our prospective single institution trial is to examine the predictive value of a standardized vacuum assisted core-needle biopsy (VAB) of the tumor site after neoadjuvant therapy with respect to pathologic response status. Methods: From 2011-2017, all patients who had completed neoadjuvant breast cancer therapy at our institution were informed about this trial regardless of their clinical response status. In case of consent, a VAB of the clip-marked tumor site was performed directly before the operation. At least 3, in most cases 6 biopsy cylinders were obtained. Results: A total of 113 patients completing neoadjuvant therapy consented to the trial. Four patients presented with bilateral breast cancer, resulting in 117 cases of breast cancer. The pCR rate (ypT0ypN0) was 36% (n=42). In 14 cases, the biopsy did not show any sign of residual disease, although residual disease was detected upon operation, resulting in an accuracy of 88% for correct prediction of pathologic response. Pre-operative VAB correctly predicted residual tumor in 81%. The negative predictive value was 75%. Conclusions: Although the results of this trial are encouraging, a false negative rate of 19% is entirely insufficient. The method may be useful in guiding decisions regarding the modification of neoadjuvant therapy based on pathological response. Whether or not correct prediction of pathologic response may be improved by further standardizing the tumor marking procedure as well as better defining and increasing the volume of tissue removal by VAB should be examined in a further prospective trial. The omission of operative therapy in case of pCR in a preoperative biopsy after completion of NACT cannot be recommended. Citation Format: Regina Große, Antonia Lebioda, Jana Saegenschnitter, Tin Dao Nguyen, Holger Zentgraf, Joerg Buchmann, Christine Fathke, Susanne Steer, Christoph Thomssen. Vacuum assisted core-needle biopsy after neoadjuvant therapy in breast cancer to predict the status of pathologic response [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-03-01.
Visualization of T Cell Migration in the Spleen Reveals a Network of Perivascular Pathways that Guide Entry into T Zones
Authors: Anne Chauveau, Gabriela Pirgova, Hung-Wei Cheng, Angelina De Martin, Felix Y. Zhou, Sarah Wideman, Jens Rittscher, Burkhard Ludewig, Tal I. Arnon
Journal: Immunity (2020)

Lymphocyte homeostasis and immune surveillance require that T and B cells continuously recirculate between secondary lymphoid organs. Here, we used intravital microscopy to define lymphocyte trafficking routes within the spleen, an environment of open blood circulation and shear forces unlike other lymphoid organs. Upon release from arterioles into the red pulp sinuses, T cells latched onto perivascular stromal cells in a manner that was independent of the chemokine receptor CCR7 but sensitive to Gi protein-coupled receptor inhibitors. This latching sheltered T cells from blood flow and enabled unidirectional migration to the bridging channels and then to T zones, entry into which required CCR7. Inflammatory responses modified the chemotactic cues along the perivascular homing paths, leading to rapid block of entry. Our findings reveal a role for vascular structures in lymphocyte recirculation through the spleen, indicating the existence of separate entry and exit routes and that of a checkpoint located at the gate to the T zone.
Abstract 113: Readmission Rates and Causes for In-Hospital Cardiac Arrest Survivors at 30 and 180 Days: Insights from Nationwide Readmission Database
Authors: Ahmed Elkaryoni, Paul Chan
Journal: Circulation (2019)

Introduction: Rates of survival to discharge for patients with in-hospital cardiac arrest (IHCA) have improved over the past 2 decades from 13% in 2000 to 25% in 2016. Yet, little is known about rates and causes of readmissions among those survivors. We sought to investigate early and late rates and causes of readmission for IHCA survivors at 30 and 180 days after discharge. Methods: Within the Nationwide Readmission Database (NRD), we identified patients 18 years of age or older who survived to hospital discharge after an IHCA between 2010 and 2016. IHCA was defined by an ICD-9 or ICD-10 diagnosis code (cardiac arrest, ventricular fibrillation or flutter) combined with a procedure code (defibrillation or external chest compression). We evaluated rates and causes of 30 and 180 days readmission and examined whether these have changed over time. Results: A total of 86,140 patients had an IHCA and survived to hospital discharge. Overall, mean age was 64.3 ± 14.9, women were 40.1%, and the mean length of stay was 15.1 ±17.9 days. All-cause readmission rates at 30 and 180 days were 22.7% and 69.9%, respectively. Readmission rates decreased over time. Thirty-day readmission rates decreased from 23.8% in 2010 to 21.1% in 2016, and 180-day readmission rates decreased from 76.1% to 63.6%. (Figure) Among readmitted patients, 13.5% were readmitted more than once at 30 days and 44.9% were readmitted more than once at 180 days. The most common cause of 30-day readmissions were congestive heart failure (11.7%), infection/septicemia (11.4%), and cardiac dysrhythmias (5.3%),whereas the top causes of 180-day readmissions were congestive heart failure (11.9%), infection/septicemia (11.3%), and respiratory insufficiency, or device complications (4.6%). Conclusion: All-cause readmission rates for IHCA survivors at 30 and 180 days have decreased over time, Congestive heart failure is the most common cause of readmissions but accounts for only 11.7% and 11.9% of readmissions at 30 and 180 days.
Wee1 Kinase Inhibitor AZD1775 Effectively Sensitizes Esophageal Cancer to Radiotherapy
Authors: Linlin Yang, Changxian Shen, Cory J. Pettit, Tianyun Li, Andrew J. Hu, Eric D. Miller, Junran Zhang, Steven H. Lin, Terence M. Williams
Journal: Clinical Cancer Research (2020)

Esophageal cancer is a deadly malignancy with a 5-year survival rate of only 5% to 20%, which has remained unchanged for decades. Esophageal cancer possesses a high frequency of
DeepMILO: a deep learning approach to predict the impact of non-coding sequence variants on 3D chromatin structure
Authors: Tuan Trieu, Alexander Martinez-Fundichely, Ekta Khurana
Journal: Genome biology (2020)

Abstract Non-coding variants have been shown to be related to disease by alteration of 3D genome structures. We propose a deep learning method, DeepMILO, to predict the effects of variants on CTCF/cohesin-mediated insulator loops. Application of DeepMILO on variants from whole-genome sequences of 1834 patients of twelve cancer types revealed 672 insulator loops disrupted in at least 10% of patients. Our results show mutations at loop anchors are associated with upregulation of the cancer driver genes BCL2 and MYC in malignant lymphoma thus pointing to a possible new mechanism for their dysregulation via alteration of insulator loops.
Nab-028, a nanoparticle albumin-bound novel taxane, shows improved efficacy and lower toxicity over the tween formulation (Tween-028)
Authors: Tapas De, Jean Veith, Ralph J. Bernacki, Patrick Soon-Shiong, Neil Desai
Journal: Cancer Research (2005)

1432  Background: ABI-028 is a novel taxane selected for its lack of cross-resistance in tumor cell lines expressing the multidrug resistant phenotype (MDR/Pgp) and inhibition of P-glycoprotein (Pgp). Due to its hydrophobicity, ABI-028 can be formulated in the surfactant Tween 80 (same vehicle as Taxotere). However, removal of surfactants from taxane formulations e.g., in the case of nanoparticle albumin-bound (nab) paclitaxel (Abraxane™) have demonstrated improvements in safety and efficacy over their surfactant containing counterparts (O’Shaughnessy, SABCS 2003). Tween 80 also strongly inhibited the binding of the taxane, paclitaxel, to albumin, possibly compromising albumin based drug transport via the gp60 receptor on microvessel endothelial cells (Desai, EORTC-NCI-AACR, 2004). Herein, we compared the toxicity and antitumor efficacy of Tween-028 vs a 50% higher dose of nab-028. Methods: Nanoparticle nab-028 was prepared using nab technology and characterized by laser light scattering. Nab-028 and Tween-028 were tested against Pgp+ DLD-1 (known to be resistant against paclitaxel and docetaxel - Vredenburg et al, JNCI 93: 1234-1245, 2001) human colon carcinoma xenograft in nude mice (n=5/group) at doses of 50 mg/kg (Tween-028, previously established as MTD) and 75 mg/kg (nab-028) given q3dx4, i.v. Control groups of PBS and human serum albumin (HSA) were also used. Results: Nab-028 yielded nanoparticles with mean size, ZAve=119 nm and Zeta potential = -32.7 mV. Nab-028 was lyophilized to a dry powder that easily dispersed in saline. In vivo, there was significantly more weight loss (ANOVA, p
Evaluation of Sex-Specific Incidence of Melanoma
Authors: Catherine M. Olsen, John F. Thompson, Nirmala Pandeya, David C. Whiteman
Journal: JAMA Dermatology (2020)

Men and women develop melanoma at different rates on different body sites, with variation across countries, but explanations for these disparities remain elusive.To test whether observed differences in melanoma incidence between men and women vary by population, age, or anatomic site.Cross-sectional analysis of sex- and site-specific temporal trends in melanoma incidence over 3 decades was conducted for men and women diagnosed with invasive melanoma in the US (limited to white race), Canada, Australia, New Zealand, the UK, Sweden, Norway, and Denmark. Using cancer registry data, male to female incidence rate ratios (IRRs) were calculated overall and by anatomic site, and Joinpoint regression models were used to estimate the annual percentage rate changes in sex- and site-specific incidence in each population. Incidence rates were standardized to the US 2000 population. Data on the incidence between January 1, 1982, and December 31, 2015, were obtained; analysis was conducted from March 1 to October 15, 2019.Male to female IRRs and annual percentage change in rates.Total melanoma incidence was higher in men than women in US individuals (limited to white race), Canada, Australia, and New Zealand, but not in Denmark, the UK, Norway, and Sweden. In all populations, men had higher rates of melanoma of the head and neck and trunk than women (male to female IRR >1), but lower melanoma rates on the lower limbs (ie, male to female IRR approximately 0.5). The male to female IRR increased log linearly with age, with excess melanomas in women younger than 45 years in all populations (eg, IRR for 20-24 y age group, 0.3 in Denmark and 0.7 in Australia), and excess melanomas in men older than 69 years (eg, IRR for 70-74 y age group, 1.1 in Denmark and 2.1 in the US white population). The age at which the melanoma incidence in men exceeded the melanoma incidence in women differed by population, being achieved the earliest in Australia (45-49 years) and latest in Denmark (65-69 years).In predominantly fair-skinned populations, melanoma incidence appears to differ systematically and consistently between men and women by age and anatomic site.
Abstract P1-20-27: Changes in the shoulder range of motion, strength after breast cancer surgery: An observational study
Authors: Jihee Min, Sujin Yeon, Jinjoo Min, Jee Ye Kim, Seung Il Kim, Ha-Nui Park, Jeong min Lee, Justin Y. Jeon
Journal: Cancer Research (2020)

Abstract Purpose: The importance of rehabilitation after breast surgery is valued, yet changes in range of motion (ROM) and shoulder strength after surgery have not been elucidated. The aim of this study was to explore the shoulder ROM and strength in both surgery (SS) and non-surgery side (NSS) after breast cancer surgery for up to four weeks. Methods: Twenty-five patients (7 total mastectomy, 18 partial mastectomy) were observed five times: the day before surgery, on discharge day (post operate day; POD 1 or 2), the 1st outpatient visit (POD 7-10), the 2nd outpatient visit (POD 14-15), and 3rd outpatient visit (POD 21-25). The primary outcomes were ROM and strength of both the SS and NSS. Results: While ROM declined only in the shoulder of the SS, shoulder strength declined in both SS and NSS. Greatest reduction in shoulder strength was observed in flexion (SS: -43.9% to -45.3%, NSS: -14.2% to -35.8%) and abduction in both SS and NSS (SS: -41.1% to -52.5%, NSS: -16.3% to -30.6%). Shoulder strength on the SS decline immediately after surgery, which remained low after four weeks. Shoulder strength of the NSS continually declined after surgery up to four weeks. Conclusion:These results provide preliminary evidence for clinicians to understand the changes of shoulder ROM, strength, and function after surgery in breast cancer patients. Rehabilitation exercises should be implemented in both SS and NSS. Citation Format: Jihee Min, Sujin Yeon, Jinjoo Min, Jee Ye Kim, Seung Il Kim, Ha-Nui Park, Jeong min Lee, Justin Y. Jeon. Changes in the shoulder range of motion, strength after breast cancer surgery: An observational study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-27.
Abstract P5-07-14: Chronic kidney disease in breast cancer treatment and survival
Authors: Deirdre A Hill, Christos Argyropoulos, Maria-Eleni Roumelioti, Mark Unruh
Journal: Cancer Research (2020)

Abstract Background: Presence of chronic kidney disease (CKD Stages 3-5) prior to breast cancer diagnosis may increase the risk of mortality among women with invasive breast cancer. However, the evidence base is limited, and the magnitude of this mortality risk is unknown. Breast cancer therapy may also be altered by presence of CKD. We sought to understand the role of CKD in breast cancer survival, with particular attention to receipt of recommended treatment. Methods: All women diagnosed with invasive breast cancer from 1992-2016 in 18 SEER-Medicare sites (age 66 or older; n= 168701) were evaluated for breast cancer-specific mortality (BCSM) using multivariate Cox models, with estimation of hazard ratios (HR) and 95% confidence intervals (CI). All analyses were adjusted for age, race/ethnicity, diagnosis year, tumor characteristics, and socioeconomic factors, and also for diabetes, myocardial infarction, and congestive heart failure prior to diagnosis. Separate analyses were run according to receipt vs non-receipt of standard of care for breast cancer treatment (defined according to National Comprehensive Cancer Network (NCCN) guidelines. Results: Median follow-up was 63 months (26 months with CKD). Women with CKD were at increased risk of BCSM (CKD Stage 3: HR 1.2; 95% CI 1.0-1.5; CKD Stage 4 HR 1.7; 95% CI 1.3-2.2; CKD Stage 5/End Stage Renal Disease HR 1.5; 95% CI 1.1-2.1), compared to women without CKD. In analyses of any CKD, restricted to women who met NCCN guideline therapy recommendations, women had an elevated risk of BCSM regardless of whether they did (HR 1.6; 95% CI 1.1-2.1) or did not (HR 1.4; 95% CI 1.0-1.8) receive recommended chemotherapy, and whether they did (HR 1.6; 95% CI 1.1-2.3) or did not (HR 1.3; 95% CI 0.9-2.0) receive recommended radiotherapy. Discussion: Women with CKD have an increased risk of breast cancer mortality regardless of receipt of guideline-based treatment. CKD is underascertained in Medicare claims data, thus the reported results (likely underestimates) will be presented with sensitivity analyses. CKD may influence breast cancer outcomes due to associated systemic inflammation and comorbid conditions, as well as release of soluble mediators such as cytokines, chemokines, growth factors, and factors involved in remodeling of the extracellular matrix and epithelial-mesenchymal transition. As such factors involved in CKD progression also influence cancer, increased understanding may provide clues to ameliorate adverse outcomes in both disease entities. Citation Format: Deirdre A Hill, Christos Argyropoulos, Maria-Eleni Roumelioti, Mark Unruh. Chronic kidney disease in breast cancer treatment and survival [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-07-14.
Organoid cultures of early-onset colorectal cancers reveal distinct and rare genetic profiles
Authors: Helen H N Yan, Hoi Cheong Siu, Siu Lun Ho, Sarah S K Yue, Yang Gao, Wai Yin Tsui, Dessy Chan, April S Chan, Jason W H Wong, Alice H Y Man, Bernard C H Lee, Annie S Y Chan, Anthony K W Chan, Ho Sang Hui, Arthur K L Cheung, Wai Lun Law, Oswens S H Lo, Siu Tsan Yuen, Hans Clevers, Suet Yi Leung
Journal: Gut (2020)

Objective Sporadic early-onset colorectal cancer (EOCRC) has bad prognosis, yet is poorly represented by cell line models. We examine the key mutational and transcriptomic alterations in an organoid biobank enriched in EOCRCs. Design We established paired cancer (n=32) and normal organoids (n=18) from 20 patients enriched in microsatellite-stable EOCRC. Exome and transcriptome analysis was performed. Results We observed a striking diversity of molecular phenotypes, including PTPRK-RSPO3 fusions. Transcriptionally, RSPO fusion organoids resembled normal colon organoids and were distinct from APC mutant organoids, with high BMP2 and low PTK7 expression. Single cell transcriptome analysis confirmed the similarity between RSPO fusion organoids and normal organoids, with a propensity for maturation on Wnt withdrawal, whereas the APC mutant organoids were locked in progenitor stages. CRISPR/Cas9 engineered mutation of APC in normal human colon organoids led to upregulation of PTK7 protein and suppression of BMP2 , but less so with an engineered RNF43 mutation. The frequent co-occurrence of RSPO fusions with SMAD4 or BMPR1A mutation was confirmed in TCGA database searches. RNF43 mutation was found in organoid from a leukaemia survivor with a novel mutational signature; and organoids with POLE proofreading mutation displayed ultramutation. The cancer organoid genomes were stable over long culture periods, while normal human colon organoids tended to be subject to clonal dominance over time. Conclusions These organoid models enriched in EOCRCs with linked genomic data fill a gap in existing CRC models and reveal distinct genetic profiles and novel pathway cooperativity.
Abstract P4-04-09: The acquired resistance of mammary cancer cells to CDK4/6 inhibitors drives a DNA methylation reprogramming of genes encoding for BCL2 family members that confers a phenotype of high apopto-sensitivity induced by a BH3-mimetic drug
Authors: Jean-Sebastien FRENEL, Deborah Voisin, Arulraj Nadaradjane, Gwenola Bougras-Catron, Mario Campone, Aurelien Serandour, Pierre-Francois Cartron
Journal: Cancer Research (2020)

Abstract Introduction. Due to the aberrant deregulation of the CDK4/6-INK4-RB pathway in breast cancer, CDK4/6 inhibitors are now a cornerstone of first line treatment of metastatic breast cancer showing an increase of progression free survival and overall survival. However, resistance to treatment eventually occur. We aimed at deciphering the molecular mechanisms of resistance to CDK4-6 inhibitors and at evaluating associations of therapies that could restore the sensitivity to the treatment. Methods. To identify potential DNA methylation signatures associated with the acquired resistance to CDK4/6 inhibitors, we established a MCF7 model, resistant to CDK4/6 inhibitors that we also used in Swiss nude mice via xenograft experiments. qMSRE were used to analyze the methylation status of genes encoding for BCL2 family members in cells, but also on circulating tumor DNA (ctDNA) in our in vivo model. Results. Using acquired resistant MCF7 cells to CDK4/6 inhibitors, our work demonstrate that these cells harbor a phenotype of high apopto-sensitivity induced by a BH3-mimetic drug. We next discern that DNMT3A and TET2 are the molecular determinants of this phenomenon via the epigenetic modulation of DNA methylation profile of genes encoding for BCL2 family. Using in vivo model, we noted that the ctDNA dynamic of the DNA methylation level of genes encoding for BCL2 family members is associated with the emergence of the resistance to CDK4/6 inhibitor demonstrated by the absence of tumor growth inhibition. Our experiments also indicated that the administration of a BH3-minetic drug at this time point restores the inhibition of tumor growth. Conclusion. This work provides the evidence that epigenetic modulation (methylation level) of key genes detected in ctDNA is associated with resistance to CDK4-6 inhibitors. The BH3-mimetic drugs are seem really appealing in that context. Citation Format: Jean-Sebastien FRENEL, Deborah Voisin, Arulraj Nadaradjane, Gwenola Bougras-Catron, Mario Campone, Aurelien Serandour, Pierre-Francois Cartron. The acquired resistance of mammary cancer cells to CDK4/6 inhibitors drives a DNA methylation reprogramming of genes encoding for BCL2 family members that confers a phenotype of high apopto-sensitivity induced by a BH3-mimetic drug [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-04-09.
Utility of prothrombin complex concentrate as first-line treatment modality for coagulopathy in patients undergoing liver transplantation: A propensity score-matched study
Authors: Piyush Srivastava, Anil Agarwal, Amit Jha, Suvyl Rodricks, Kausar Makki, Ashish Singhal, Vivek Vij
Journal: International Journal of Surgery (2020)
Noninvasive markers (ALBI and APRI) predict post-hepatectomy liver failure in patients with hepatocellular carcinoma
Authors: Jin-yu Shi, Li-yang Sun, Bing Quan, Hao Xing, Chao Li, Lei Liang, Timothy M. Pawlik, Ya-hao Zhou, Hong Wang, Wan Yee Lau, Feng Shen, Tian Yang
Journal: International Journal of Surgery (2020)
Tumor cells suppress radiation-induced immunity by hijacking caspase 9 signaling
Authors: Chuanhui Han, Zhida Liu, Yunjia Zhang, Aijun Shen, Chunbo Dong, Anli Zhang, Casey Moore, Zhenhua Ren, Changzheng Lu, Xuezhi Cao, Chun-Li Zhang, Jian Qiao, Yang-Xin Fu
Journal: Nature Immunology (2020)
Covid-19: Patients who are improving could have treatment withdrawn if others could benefit more
Authors: Elisabeth Mahase
Journal: BMJ (2020)

The heat shock protein 90 (Hsp90) chaperone functions as a protein-folding buffer and plays a unique role promoting the evolution of new heritable traits. To investigate the role of Hsp90 in modulating protein synthesis, we screened more than 1200 proteins involved in mRNA regulation for physical interactions with Hsp90 in human cells. Among the top hits was CPEB2, which strongly binds Hsp90 via its prion domain, reminiscent of the prion-like regulation of translation of <i>Aplysia</i> CPEB. In a yeast model of CPEB prion-dependent translation regulation, transient inhibition of Hsp90 amplified CPEB2 prion activity and resulted in persistent translation of the CPEB reporter. Remarkably, inhibition of Hsp90 was sufficient to induce a heritable change in protein translation that persisted for 30 generations, even in the absence of exogenous CPEB. Although we identified a variety of perturbations that enhanced translation of the reporter, only Hsp90 inhibition led to persistent activation. Thus, transient loss of Hsp90 function leads to the non-genetic inheritance of a novel translational state. We propose that, in addition to sculpting the conformational landscape of the proteome, Hsp90 promotes phenotypic variation by modulating protein synthesis.