bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A49: Viable circulating ensembles of tumor-associated cells persist in pretreated patients with solid organ cancers showing no radiologically detectable disease
Authors: Limaye Sewanti A. , Crook Timothy , Akolkar Dadasaheb , Patil Darshana , Devhare Pradip , Patil Revati , Patel Shoeb , Khan Shabista , Dhasarathan Raja , Datta Vineet , Sims Cynthe , Srinivasan Ajay , Datar Rajan
Published: June 2020

The success of treatment in solid organ cancers is ascertained by radiologic imaging as per standard-of-care protocol, with PET-CT being the modality of choice. However, even in cases where complete resolution of the disease is noted radiologically, recurrence or emergence of new metastases is not uncommon. To explore the underlying cause of such recurrence, we hypothesized that circulating metastatic disease (CMD) in the nature of viable tumor cells or clusters would be a persistent systemic feature of solid organ cancers, although there may be no overt evidence of disease. We identified 1,217 patients with known and previously treated cases of various solid organ cancers (metastatic and nonmetastatic), where a recent PET-CT scan showed no radiologic evidence of disease. 15 mL peripheral blood was collected from these patients. Peripheral blood mononuclear cells (PBMCs) were harvested by centrifugation. Circulating ensembles of tumor-associated cells (C-ETACs) were enriched from PBMCs using an epigenetically acting stabilization process, which is cytotoxic towards nonmalignant cells but confers survival privilege on apoptosis-resistant cells of tumorigenic origin as well as their heterotypic clusters (C-ETACs). C-ETACs were characterized by immunostaining for EpCAM, pan-CK, and CD45 as well as for organ-specific markers. Among the 1,217 patients with no radiologic evidence of disease, C-ETACs were detected in 1,118 (91.9%) and were confirmed by immunostaining. In a subset analysis, C-ETACs from 80 samples were immunostained for organ- or subtype-specific antigens including those from head and neck (P63), breast (GCDFP15), colorectum (CDX2), liver (Hep Par-1), ovary (CA125), prostate (PSMA), cervical (P63), and lung (TTF-1/Napsin-A). Circulating metastatic disease (CMD) in the form of viable C-ETACs is a potent threat in patients with solid organ cancers despite complete radiologic response to treatment.

Citation Format: Sewanti A. Limaye, Timothy Crook, Dadasaheb Akolkar, Darshana Patil, Pradip Devhare, Revati Patil, Shoeb Patel, Shabista Khan, Raja Dhasarathan, Vineet Datta, Cynthe Sims, Ajay Srinivasan, Rajan Datar. Viable circulating ensembles of tumor-associated cells persist in pretreated patients with solid organ cancers showing no radiologically detectable disease [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A49.
Abstract A56: Identification of circulating miRNA signatures in rectal cancer
Authors: Cervena Klara , Opattova Alena , Pardini Barbara , Naccarati Alessio , Vodicka Pavel , Vymetalkova Veronika
Published: June 2020

Colorectal cancer is the third most common cancer and the second leading cause of cancer death in Europe. Therefore, the search for new biomarkers to enable facilitate early diagnosis, prognosis, and individualized treatment is particularly warranted. From a clinical point of view, malignancies in the colon and the rectum (RC) present two distinct entities that require different treatment strategies, so CRC might not be considered as a single enteropathogenic entity. MicroRNA (miRNAs) are small noncoding RNA molecules involved in the post-transcriptional and translational regulation of gene expression. The discovery that miRNAs may act either as oncogenes or tumor suppressors has initiated extensive research. It was recently discovered that extracellular miRNAs circulate in the bloodstream and that such circulating miRNAs are remarkably stable. This has raised the possibility that miRNAs might serve as novel markers for disease diagnosis and prognosis. In the present study, we aimed to identify circulating miRNAs enabling early diagnosis and prognosis of RC. MiRNA expression levels (from plasma and plasma exosomes) were characterized by next-generation sequencing (NGS) in 24 patients with RC collected at 2-time intervals. The first sampling was collected at the time of diagnosis and the second sampling was conducted around 1 year after the diagnosis. The expression levels of miR-122 and miR-142 were identified to be associated with overall survival in RC patients. Their functional characteristics were tested in vitro on rectal cancer cell lines HRA16 and SW1463. Increased levels of miRNAs were associated with decreased long-term survival of cells. Identified miRNAs are currently being verified on a larger population of RC patients. This has raised the question whether miRNA can serve as biomarkers for rectal cancer, but prior to its clinical applications, clinical trials are warranted. Acknowledgments: This work was supported by AZV 17-30920A, GA17-16857S, and GA UK 302119.

Citation Format: Klara Cervena, Alena Opattova, Barbara Pardini, Alessio Naccarati, Pavel Vodicka, Veronika Vymetalkova. Identification of circulating miRNA signatures in rectal cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A56.
Abstract B28: Large and polymorphonuclear circulating cancer-associated cell with dual epithelial and macrophage/myeloid phenotype as a liquid biomarker in non-small cell lung cancer patients
Authors: Manjunath Yariswamy , Avella Diego M. , Kimchi Eric T. , Staveley-O'Carroll Kevin F. , Deroche Chelsea B. , Li Gunagfu , Kaifi Jussuf T.
Published: June 2020

Purpose: In addition to the FDA-approved definition of a circulating tumor cell (CTC), various phenotypes of circulating cancer-associated cells in the blood have been described. A distinct large (>30μm), polymorphonuclear, circulating, cancer-associated cell (CCAC) with a dual epithelial and macrophage/myeloid phenotype has been identified in solid cancer patients. The goal of the study was to identify and further characterize these hybrid CCACs in non-small cell lung cancer (NSCLC) patients.

Experimental Design: In a prospective trial, 7.5 mL of peripheral blood was collected from 167 subjects. CTCs and CCACs were isolated by size-based exclusion with a microfilter and immunofluorescence staining was performed (cytokeratin (CK) 8/18/19, EpCAM, CD14/45, DAPI).

Results: 78 NSCLC patients and 89 control subjects (69 chronic smokers with and without lung nodules on screening LDCT, 20 healthy never-smokers) were enrolled. Distinct, large, polymorphonuclear CKpos/EpCAMpos/CD14/45pos CCACs were detected at lower rates than traditional CKpos/EpCAMpos/CD45negCTCs, but significantly higher in subjects with NSCLC in comparison to controls (p<0.05). These cells and traditional CTCs were absent in 20 healthy controls. In contrast to CTCs, counts of large and polymorphonuclear CCACs were not associated with tumor stages. However, ≥2 CCACs correlated with significantly poorer survival and higher recurrence rates by uni- and multivariate analysis (p<0.05).

Conclusions and Future Perspectives: This study shows that in addition to CTCs, a distinct, large, polymorphonuclear CCAC with a dual epithelial and macrophage/myeloid phenotype is associated with an aggressive clinical behavior in NSCLC patients. The biologic role of these unique cells will need to be further investigated, as these may have a potential impact on the immune response towards the cancer.

Citation Format: Yariswamy Manjunath, Diego M. Avella, Eric T. Kimchi, Kevin F. Staveley-O'Carroll, Chelsea B. Deroche, Gunagfu Li, Jussuf T. Kaifi. Large and polymorphonuclear circulating cancer-associated cell with dual epithelial and macrophage/myeloid phenotype as a liquid biomarker in non-small cell lung cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B28.
Abstract B34: The number of tumorspheres cultured from peripheral blood is directly related to presence of metastasis in breast cancer patients
Authors: Pizon Monika , Schott Dorothea , Pachmann Ulrich , Pachmann Katharina
Published: June 2020

Background: Cancer stem cells (CSCs) are the critical subpopulation of cancer cells involved in tumor formation, progression, metastasis, and drug resistance. CSCs also have been considered the main cause of cancer recurrence, and the identification of targets and biomarkers is still under development. In this study, primary cultures from peripheral blood were established, using sphere-forming assays for CSC enrichment, and correlated with clinicopathologic features.

Methods: Circulating cancer stem cells were cultured under conditions favoring growth of tumorspheres from 72 patients with breast cancer, including a subpopulation of 23 patients with metastatic disease. Cell viability, stem cell marker expression, and ALDH 1 activity were evaluated by fluorescence scanning microscope (Olympus Scan®R).

Results: Sphere formation was observed in 79% of patients with breast cancer. In the current study we found that the number of tumorspheres depended on stage of disease. Patients with metastatic disease had statistically significantly more tumorspheres compared to patients without metastasis (median 30 vs. 10; p=0.002). Furthermore, patients with multiple metastases had more tumorspheres as compared to patients with single metastasis (median 30 vs. 60; p<0.05). Analysis of surface marker expression profile of tumorspheres cultured from peripheral blood showed that spheres had typical phenotype of cancer stem cells with a high enzymatic activity for ALDH 1. There was no sphere formation in a control group with 20 healthy donors.

Conclusion: Identifying the circulating cancer stem cell may provide more clinically useful prognostic information and can be the basis for developing novel therapies.

Citation Format: Monika Pizon, Dorothea Schott, Ulrich Pachmann, Katharina Pachmann. The number of tumorspheres cultured from peripheral blood is directly related to presence of metastasis in breast cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B34.
Abstract B39: Changes in the number of residual circulating epithelial tumor cells (CETCs) and their programmed cell death ligand 1 (PD-L1) status during radiotherapy in breast cancer patients
Authors: Schott Dorothea , Pizon Monika , Pachmann Katharina , Pachmann Ulrich , Maeurer Matthias
Published: June 2020

Background: Preclinical studies have suggested that radiotherapy (RT) followed by immunotherapy could be a promising strategy for synergistic enhancement of treatment efficacy. RT induces immunogenic changes in cancer cells that can lead to adaptive upregulation of PD-L1 expression. Moreover, RT not only reduces local recurrence but also improves overall survival by preventing distant metastases, which indicates its influence on the remaining occult tumor, such as circulating tumor cells. For this reason, the aim of this study was to determine the PD-L1 status on CETCs before and during RT.

Methods: CETCs were determined in 54 primary breast cancer patients in early and locally advanced stages. The number of CETCs and their expression of PDL-L1 were investigated using the maintrac method. The fraction of PD-L1 positive CETCs was assessed prior to (baseline), 3 and 6 weeks after the start of RT.

Results: We found a correlation between the PD-L1 status of CETCs and aggressiveness of cancer disease prior to radiotherapy. Patients with positive lymph node status presented more PD-L1 positive CETCs compared to patients with negative lymph nodes (mean 73% vs. 50%, p<0.01). Moreover, the HER2 expression of the primary tumor was also positively correlated with PD-L1 expression. Lower numbers of CETCs were detected in patients who had not received chemotherapy or adjuvant chemotherapy before RT than in those who received neoadjuvant chemotherapy (median 20 vs. 25 vs. 120 CETC/100μL blood, p<0.001). Surprisingly, the fraction of PD-L1 positive CETCs decreased during radiotherapy only in patients who had received neoadjuvant chemotherapy.

Conclusion: Although the number of CETCs and the fraction of PD-L1 positive CETCs were higher in patients who had received neoadjuvant chemotherapy, radiotherapy reduced both measured biomarkers. In the future PD-1/PD-L1 checkpoint inhibitors after radiotherapy might have additional benefit in breast cancer patients.

Citation Format: Dorothea Schott, Monika Pizon, Katharina Pachmann, Ulrich Pachmann, Matthias Maeurer. Changes in the number of residual circulating epithelial tumor cells (CETCs) and their programmed cell death ligand 1 (PD-L1) status during radiotherapy in breast cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B39.
Abstract B53: Extracellular vesicle-based liquid biopsy via lipid-based nanoprobes
Authors: Zheng Siyang , He Hongzhang , Wang Faming , Wan Yuan
Published: June 2020

Extracellular vesicles (EVs) can mediate intercellular communication by transferring cargo proteins and nucleic acids between cells. The pathophysiologic roles and clinical value of EVs are under intense investigation, yet most studies are limited by technical challenges in the isolation of nanoscale EVs (nEVs). Here, we report a lipid-nanoprobe system that enables spontaneous labeling of nEVs for subsequent magnetic enrichment in 15 minutes, with isolation efficiency and cargo composition similar to what can be achieved by the much slower and bulkier method of ultracentrifugation. We also show that this approach allows for downstream analyses of nucleic acids and proteins, enabling the identification of EGFR and KRAS mutations following nEV isolation from the blood plasma of non-small cell lung cancer patients. The efficiency and versatility of the lipid-nanoprobe approach open up opportunities in point-of-care cancer diagnostics.

Citation Format: Siyang Zheng, Hongzhang He, Faming Wang, Yuan Wan. Extracellular vesicle-based liquid biopsy via lipid-based nanoprobes [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B53.
Abstract B61: Encyclopedic noninvasive liquid biopsies for differential diagnosis in prostate cancer
Authors: Patil Darshana A. , Akolkar Dadasaheb , Patil Revati , Fulmali Pooja , Fulmali Pradip , Ainwale Akshay , Srivastava Navin , Datta Vineet , Sims Cynthe , Srinivasan Ajay , Datar Rajan
Published: June 2020

Differential diagnosis of prostatic adenocarcinomas is based on histopathologic analysis of tumor tissue obtained by transrectal ultrasound (TRUS)-guided biopsies. However, such invasive biopsies are associated with pain, procedural expenses, sequelae, and risk of complications. Though immunocytochemistry (ICC) profiling of circulating tumor cells (CTCs, defined as EpCAM+, panCK+, CD45-) has been previously attempted for diagnosis in some cancers, it has been unviable due to limited yields of CTCs. For the first time we used enrichment of CTCs that permit meaningful ICC profiling for diagnosis of prostate cancers in suspected cases as contradistinguished from cases of benign enlargement of prostate (BEP). We obtained 15 mL of venous blood draw from 650 individuals, of whom 65 had a confirmed diagnosis of either prostate adenocarcinoma and 585 were diagnosed with benign prostate hyperplasia. CTCs were enriched from PBMCs fraction using an epigenetically acting enrichment process that is lethal towards normal (nonmalignant) cells but confers survival privilege on apoptosis-resistant CTCs. Harvested CTCs were confirmed by immunostaining for EpCAM and pan-CK. ICC profiling of these CTCs was also performed with organ-specific markers PSMA and AMACR. Viable CTCs could be obtained from 58 samples (89.2%) out of 65 confirmed prostate cancer cases. Among the 40 samples that were characterized by deep ICC profiling, all samples (100%) were positive for PSMA and AMACR. Among the benign cases, CTCs were observed in 10 samples (1.7%), of which all 10 were positive for PSMA but negative for AMACR. These patients are being followed up. Possibility of other cancers is not ruled out in these patients. Our results show that ICC-based characterization of CTCs can provide necessary diagnostic information noninvasively to substitute for conventional procedures dependent on tissue extraction.

Citation Format: Darshana A. Patil, Dadasaheb Akolkar, Revati Patil, Pooja Fulmali, Pradip Fulmali, Akshay Ainwale, Navin Srivastava, Vineet Datta, Cynthe Sims, Ajay Srinivasan, Rajan Datar. Encyclopedic noninvasive liquid biopsies for differential diagnosis in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B61.
Abstract IA11: Clinical applications of liquid biopsy in multiple myeloma
Authors: Trudel Suzanne , Pugh Trevor
Published: June 2020

Multiple myeloma (MM) is characterized by recurrent cytogenetic and molecular abnormalities that have the potential to profoundly impact therapeutic decisions. Conventional karyotyping and/or FISH cytogenetics studies have identified translocations and copy number abnormalities (CNAs) that predict clinical outcomes. More recently, MM whole-exome sequencing studies have uncovered recurrent mutations in genes associated with prognosis and others that are potentially actionable and/or implicated in drug resistance. These observations highlight the need for advanced genomic platforms to inform prognosis and therapeutic decisions.

Currently, molecular profiling of MM is performed on bone marrow (BM) aspirates; however, the genetic information obtained from aspirates is confounded by spatial and temporal intratumor genetic heterogeneity. Genomic studies of MM have confirmed the bias introduced by single-site biopsies, demonstrating that not all mutations are shared between targeted biopsies of extramedullary sites and BM. Further, longitudinal whole-genome sequencing studies have not only uncovered tumor heterogeneity at diagnosis but also subclonal competition with a shifting dominance of tumor clones and accumulation of genetic events during progression that are particularly affected by therapeutic pressures. Thus, information acquired from a single biopsy provides a spatially and temporally limited snapshot of a tumor that likely underestimates the complexity of the tumor genomic landscape.

Analysis of circulating tumor DNA (ctDNA) and in blood plasma has the potential to overcome these barriers, providing access to the genetic landscape of all cancerous lesions and allowing for noninvasive tracking of genomic evolution over time. Circulating biomarkers can provide a “liquid biopsy” alternative to tissue biopsy, providing new opportunities for treatment tailoring based on real-time monitoring from a simple blood test. Here I will discuss the current liquid biopsy technologies under evaluation for genomic characterization of multiple myeloma. I will also describe the potential clinical applications for liquid biopsies to identify patients for targeted therapies, to track genomic changes, and to follow disease burden in patients with multiple myeloma.

Citation Format: Suzanne Trudel, Trevor Pugh. Clinical applications of liquid biopsy in multiple myeloma [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA11.
Abstract IA12: Response in plasma cfDNA as an early marker of treatment effect in advanced cancer
Authors: Oxnard Geoffrey R.
Published: June 2020

Plasma cfDNA genotyping has been adopted widely as a tool for genotyping of advanced cancer at diagnosis and after treatment resistance. In addition, cfDNA genomics is a highly quantitative biomarker that could be used dynamically to evaluate the effective of a therapy. Our data point to the potential clinical meaning of changes in plasma mutation levels and support specific best practices regarding the clinical integration of this approach. In addition, these data allow us to envision a number of creative clinical applications for cfDNA-based response assessment. Finally, we must evaluate whether existing cfDNA genotyping technologies are well suited to this application, and whether new techniques must be considered in order to meet the practical requirements of a real-time clinical monitoring test.

Citation Format: Geoffrey R. Oxnard. Response in plasma cfDNA as an early marker of treatment effect in advanced cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA12.
Abstract IA14: Liquid biopsies for tracking molecular resistance in cancer
Authors: Dawson Sarah-Jane
Published: June 2020

Cell-free circulating tumor DNA (ctDNA) can be found in the bloodstream of cancer patients and is increasingly being explored as an important biomarker to monitor adaptive changes to cancer therapies. Cell-free DNA fragments from multiple lesions mix together in the peripheral blood; hence, ctDNA contains a wide representation of the genomes from multiple metastatic sites. For this reason, genome-wide analysis of ctDNA has the potential to provide an unprecedented insight into changes in the genomic landscape that occur during the development of disease and in response to cancer therapies. To date, the use of ctDNA to monitor the tumor landscape has been limited to tracking genomic evolution. However, it is now clear that cancers can also adapt to therapeutic pressure by significantly altering their transcriptome. Currently we have a limited understanding of how “nongenomic” transcriptional adaptation leads to clonal dominance or the evasion of cancer therapies. Here I will provide an overview of the use of ctDNA-based approaches to track both genomic evolution and transcriptional changes in real time to improve our understanding of the mechanisms leading to molecular resistance in cancer.

Citation Format: Sarah-Jane Dawson. Liquid biopsies for tracking molecular resistance in cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA14.
Abstract IA25: Detection of somatic mutations and HPV in saliva of patients with head and neck squamous cell carcinoma
Authors: Agrawal Nishant
Published: June 2020

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy in the world and is associated with significant morbidity and mortality. HNSCC develops in the oral cavity, pharynx, and larynx and is associated with tobacco exposure, alcohol abuse, and infection with oncogenic viruses. Despite numerous diagnostic and therapeutic advances, HNSCC often presents with advanced disease and the long-term survival for patients with HPV-negative SCC has remained ~55%. Conventional analysis of tissue through cytopathology or histopathology is the mainstay of diagnosis. There are no useful biomarkers for disease diagnosis or surveillance. The genetic landscape of HNSCC has demonstrated that these tumors are largely driven by tumor-suppressor mutations. The broad mutation spectrum detected in HNSCC by these sequencing studies not only sheds light on its molecular pathogenesis, but also serves as a molecular signature that is exquisitely specific to the individual tumor. Therefore, methods that use these molecular signatures and biomarkers and aid in improved screening/early detection, prognostication, monitoring, and surveillance are paramount for improving outcomes. We will explore tumor DNA (somatic mutations and HPV DNA) in saliva and plasma for screening, monitoring, and surveillance and outline resulting implications for personalized medicine. In HNSCC, analysis of tumor DNA has the potential to enhance tumor profiling, aid in determining patient prognosis, and guide treatment decisions.

Citation Format: Nishant Agrawal. Detection of somatic mutations and HPV in saliva of patients with head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA25.
Abstract PR02: Epigenetic biomarkers in cell-free DNA for early detection of high-grade serous ovarian carcinoma
Authors: Tew Ben Yi , Gooden Gerald , Buckley David N. , Miller Heather , Spillman Monique , Roman Lynda , Salhia Bodour
Published: June 2020

Background: High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecologic malignancy, with a 5-year survival rate of 40% or less when diagnosed with late-stage disease. There is a dramatic benefit to early diagnosis of HGSOC with a 5-year survival rate of nearly 90% for stage I disease. Unfortunately, the majority of HGSOC is diagnosed as late-stage disease and there are no reliable early screening or diagnostic tests. The objective of this study is to identify tumor-specific aberrant DNA methylation alterations detectable in circulation in order to develop a biomarker to detect early-stage HGSOC.

Methods: We performed reduced representation bisulfite sequencing (RRBS) on 33 stage 1 HGSOC tissues and 10 normal fallopian tube tissue samples from contralateral ovaries of patients with ovarian cancer. We selected the top 82 regions from RRBS for validation by targeted bisulfite amplicon sequencing in plasma. We successfully designed assays for 35 out of 82 regions. Targeted bisulfite amplicon sequencing was performed on these top 35 regions in a separate cohort of circulating tumor DNA extracted from 27 stage 1 HGSOC and 11 benign ovarian masses. We constructed a novel classifier model that we used to differentiate between patients with HGSOC and those with benign ovarian lesions.

Results: We identified 10,972 statistically significant differentially methylated regions between stage 1 HGSOC and normal fallopian tube tissues using RRBS. We then applied the classifier model on the top 35 regions determined by targeted bisulfite amplicon sequencing data on an independent cohort of plasma samples. This demonstrated that 13 of the 35 regions were able to discriminate stage 1 HGSOC from benign tumors with a high sensitivity and specificity (Area Under Curve = 0.909).

Conclusions: These novel, noninvasive biomarkers show promise as an early detection test for high-grade serous ovarian cancer.

This abstract is also being presented as Poster A08.

Citation Format: Ben Yi Tew, Gerald Gooden, David N. Buckley, Heather Miller, Monique Spillman, Lynda Roman, Bodour Salhia. Epigenetic biomarkers in cell-free DNA for early detection of high-grade serous ovarian carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr PR02.
Acute Lengthening of Progenitor Mitosis Influences Progeny Fate during Cortical Development in vivo
Authors: Mitchell-Dick Aaron , Chalem Andrea , Pilaz Louis-Jan , Silver Debra L.
Published: June 2020

Background/Aims: Prenatal microcephaly is posited to arise from aberrant mitosis of neural progenitors, which disrupts both neuronal production and survival. Although microcephaly has both a genetic and environmental etiology, the mechanisms by which dysregulation of mitosis causes microcephaly are poorly understood. We previously discovered that prolonged mitosis of mouse neural progenitors, either ex vivo or in vitro, directly alters progeny cell fate, ­resulting in precocious differentiation and apoptosis. This raises questions as to whether prolonged progenitor mitosis affects cell fate and neurogenesis in vivo, and what are the underlying mechanisms? Methods/Results: Towards addressing these knowledge gaps, we developed an in vivo model of mitotic delay. This uses pharmacological inhibition to acutely and reversibly prolong mitosis during cortical development, and fluorescent dyes to label direct progeny. Using this model, we discovered that a causal relationship between mitotic delay of neural progenitors and altered progeny cell fate is evident in vivo. Using transcriptome analyses to investigate the state of delayed cells and their progeny, we uncovered potential molecular mechanisms by which prolonged mitosis induces altered cell fates, including DNA damage and p53 signaling. We then extended our studies to human neural progenitors, demonstrating that lengthened mitosis duration also directly alters neuronal cell fate. Conclusions: This study establishes a valuable new experimental paradigm towards understanding mechanisms whereby lengthened mitosis duration may explain some cases of microcephaly.
Auditory Performance and Subjective Satisfaction with the ADHEAR System
Authors: Almuhawas Fida , Alzhrani Farid , Saleh Shaza , Alsanosi Abdulrahman , Yousef Medhat
Published: June 2020

Background: The ADHEAR device, a new nonsurgical bone conduction hearing device, has been developed for patients with conductive hearing loss. Objectives: This study aims to assess the impact of the ADHEAR device on the audiological performance and satisfaction level in subjects with conductive hearing loss. Methods: Twelve patients with conductive hearing loss were included. All patients received the device for 3 months. The audiological outcomes were determined using basic audiological assessments, including pure tone audiometry and sound field measurements of pure tone and speech audiometry with the contralateral ear occluded with a specific earplug. Additionally, the patients were subjectively evaluated using (1) the Speech, Spatial, and Qualities Questionnaire (SSQ), and (2) the custom-made ADHEAR questionnaire. Results: Analysis of the measured audiological outcomes revealed an average improvement in pure tone thresholds (functional gain) of 23 (± 4.4) dB HL when the ADHEAR system was used compared to the unaided condition in the sound field. Moreover, speech reception thresholds improved by an average of 23 (± 15.3) dB SPL in the aided condition with plugged contralateral ear. Additionally, when using ADHEAR in the sound field, subjects’ speech recognition scores improved by 32% (± 17.7) in quiet and 21% (± 15.1) in the presence of interfering noise. The average SSQ questionnaire scores improved from 3.9 at the study initiation to 6.6 after 3 months of device usage. ADHEAR custom questionnaire assessments revealed high satisfaction and acceptance of the device with no pain or skin irritation. Conclusion: During the study period, this new adhesive system yielded improved audiological outcomes with high patient satisfaction and acceptance and no reported skin irritation or pain.
Clinical Complete Response after Chemotherapy and Palliative Surgery for Unresectable Gastric Cancer
Authors: Shishida Masayuki , Toyota Kazuhiro , Ikeda Masahiro , Karakuchi Nozomi , Inoue Masashi , Saito Yasufumi , Takahashi Tadateru
Published: June 2020

Gastric cancer incidence is high in several countries, and management of advanced gastric cancer remains a challenge. Chemotherapy for unresectable gastric cancers is still evolving, and achieving a complete cure is difficult. Although a clinical complete response to chemotherapy has been reported in patients with unresectable gastric cancer, the chemotherapy duration for these patients is unclear. Here, we report the case of a 71-year-old man who presented with abdominal discomfort. Upper endoscopy revealed advanced gastric cancer on the upper gastric body. Histopathological examination revealed a poorly differentiated adenocarcinoma. Computed tomography revealed regional lymph node and multiple bilobar hepatic metastases. Radical surgery was not possible; therefore, palliative resection of the primary lesion was planned for symptomatic improvement. Tegafur, 5-chloro-2,4-dihydro­pyrimidine, and potassium oxonate were administered prior to surgery, and proximal gastrectomy was performed. Tegafur, 5-chloro-2,4-dihydropyrimidine, and potassium oxonate administration was reinitiated after surgery. A clinical complete response was achieved in the 8th postoperative month, with no hepatic metastases noted on radio imaging. Computed tomography performed in the 1st postoperative year revealed ascites; however, the cytological examination findings were negative. The initial chemotherapy was discontinued, and paclitaxel administration was commenced. Computed tomography performed annually thereafter demonstrated no recurrence, and paclitaxel was discontinued in the 9th postoperative year. The patient remained recurrence free at 12 years postoperatively. For elderly patients like the one presented here, it may be necessary to consider ceasing chemotherapy; however, because it is possible for a complete clinical response over the long term, it should be continued if the patient is well.
Adjustment of Stent Retriever Length to Clot Extent Affects First-Pass Reperfusion in Endovascular Treatment of Acute Ischemic Stroke
Authors: Styczen Hanna , Huseynov Elvin , Abdullayev Nuran , Maus Volker , Borggrefe Jan , Goertz Lukas , Onur Oezguer A. , Stockero Andrea , Mpotsaris Anastasios , Kabbasch Christoph
Published: June 2020

Background: Stent retriever technology has evolved, and significantly longer devices have become available for mechanical thrombectomy (MT) of large cerebral vessel occlusions in ischemic stroke. We hypothesized that increased stent retriever length may improve the rate of complete angiographic reperfusion and decrease the respective number of attempts, resulting in a better clinical outcome. Methods: Retrospective analysis of patients with large vessel occlusion in the anterior and posterior circulation treated with stent retriever MT. The study group was dichotomized into short (20 mm) and long (>20 mm) retrievers using propensity matching. In the anterior circulation, the clot burden score was evaluated. Primary end points were first-pass modified thrombolysis in cerebral infarction (mTICI) 3 reperfusion and first-pass mTICI ≥ 2b reperfusion, and the secondary end point was functional independence (defined as modified Rankin Scale score 0–2) at discharge and 90 days. Results: Overall, 394 patients were included in the analysis. In the anterior circulation, short stent retrievers had a significantly higher rate of first-pass reperfusion in cases with low clot burden (mTICI 3: 27% vs. 17%; p = 0.009; mTICI ≥ 2b: 42 vs. 30%; p = 0.005) and in middle cerebral artery occlusions (mTICI ≥ 2b: 51 vs. 41%; p = 0.024). Higher rates of favorable outcome at discharge and 90 days were observed for the short stent retriever group (p < 0.001). Conclusion: Stent retriever length should be adjusted to clot burden score and vessel occlusion site.
Antiproliferative Effect of Above-Label Doses of Somatostatin Analogs for the Management of Gastroenteropancreatic Neuroendocrine Tumors
Authors: Diamantopoulos Leonidas Nikolaos , Laskaratos Faidon-Marios , Kalligeros Markos , Shah Ruchir , Navalkissoor Shaunak , Gnanasegaran Gopinath , Banks Jamie , Smith Jack , Jacobs Benjamin , Galanopoulos Michail , Mandair Dalvinder , Caplin Martyn , Toumpanakis Christos
Published: June 2020

Background: Above-label doses of somatostatin analogs (SSAs) are increasingly utilized in the management of inoperable/metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), progressing on standard 4-weekly regimens. Objective: To evaluate the antiproliferative effect of 3-weekly SSA administration in a retrospective GEP-NET cohort. Methods: Patients with advanced GEP-NET, treated with long-acting release (LAR) octreotide 30 mg or lanreotide Autogel 120 mg at a 3-weekly interval, after disease progression on standard 4-weekly doses, were retrospectively identified. Clinicopathologic and treatment response data were collected. Progression-free survival (PFS; dose escalation to radiographic progression or death) was estimated with the Kaplan-Meier method. Factors associated with PFS were identified with the Cox proportional-hazards model. Results: The inclusion criteria were fulfilled by 105 patients. Octreotide LAR was administered to 60 (57%) and lanreotide Autogel to 45 (43%). Indications for dose escalation were breakthrough carcinoid symptoms (58%), radiographic progression (35%) and/or increasing biomarkers (11%). Diarrheal and/or flushing symptomatic improvement was identified in 37/67 cases (55%) and 30/55 cases (55%) with available data, respectively. The disease control rate (radiographic partial response or stable disease) was achieved in 53 patients (50%). Median PFS was 25.0 months (95% CI 16.9–33.1). Patients with radiographic progression <12 months from 4-weekly SSA initiation had worse PFS after dose escalation (7.0 vs. 17.0 months, p = 0.002). In multivariate analysis, pancreatic NETs, a Ki-67 index ≥5% and multiple extrahepatic metastases were independently associated with inferior PFS. Conclusions: Above-label doses of SSAs may offer a considerable prolongation of PFS and could be utilized as a bridge to other more toxic treatments. Patients with small bowel/colorectal primaries, a Ki-67 index <5% and absence of/limited extrahepatic metastases are more likely to benefit from this approach.
Eurytemora affinis (Poppe, 1880) (Copepoda, Calanoida) in the Gulf of Riga, Baltic Sea — elemental composition and diurnal vertical migration
Authors: Labuce Astra , Strake Solvita , Dimante-Deimantovica Inta
Published: June 2020

The present paper reports the results of two surveys conducted in the Gulf of Riga (Baltic Sea) during 1997. Elemental composition (carbon and nitrogen) and diurnal vertical migration (DVM) throughout development of the calanoid copepod Eurytemora affinis (Poppe, 1880) were studied. This is a species with a high genetic and morphological heterogeneity, inhabiting a seasonally stratified, herring (Clupea harengus Linnaeus, 1758) rich ecosystem. The DVM of copepods is a widespread advantageous behaviour, although with several trade-offs. At the expense of time spent in the food-richer surface layer, copepods avoid visual predators (planktivorous fish) by descending to greater depths, thereby decreasing their mortality. Being a part of the food web, copepods themselves serve as a source of nutrients with specific elemental contents. In the present study, we observed differences both in DVM and elemental content between the developmental stages of the studied species. The majority (57-89%) of nauplii and 1st to 3rd copepodids were found near the thermocline during daytime, whereas at night they were detected above the thermocline. The 5th stage copepodids and adults displayed evident nocturnal ascent, when most (>90%) individuals moved above 15 m depth. During daytime, they tended to disperse throughout the water column. Carbon (C%) and nitrogen (N%) in dry weight of E. affinis increased with ontogenetic development, reaching the highest values in 4th to 5th copepodids and adults. Adult males showed higher values of C% and N%, as well as an increased C : N molar ratio, compared to adult non-ovigerous females. The amount of time spent at the food-richer surface layer appeared to be related to N% in E. affinis.
A superfluous name of Premna (Lamiaceae)

Authors: WANG YINGHUI , WANG QIANG
Published: June 2020

While preparing the manuscript of Flora of Pan-Himalaya, volume 44(1) of Lamiaceae (Wang 2019), we encountered a species of the genus Premna Linnaeus (1771: 587), Premna velutina Wu (1977: 428), which was described by Wu (1977) in Flora Yunnanica, and was accepted in Flora Republicae Popularis Sinicae (Chen 1982) and Flora of China (Chen & Gilbert 1994). However, this is clearly a later homonym of Premna velutina Gürke (1895: 338). Thus, in Flora of Pan-Himalaya Vol. 44(1), a replaced name Premna wuana Wang (2019: 155) was proposed for this illegitimate name. Nonetheless, we actually made a superfluous name, since Boufford and Bartholomew (2012) had proposed Premna wui (noted as “wuii”) Boufford & Bartholomew (2012: 1) to replace the illegitimate name. We thought that all the names of Premna reported from the Pan-Himalaya region and other involved names had been dealt with in our Flora of Pan-Himalaya, volume 44(1). However, we are very sorry for ignoring the correct name Premna wui by mistake, and also for ignoring the name Premna cordiformis Li Bing Zhang & Y.F.Duan in Duan & Zhang (2014: 281), which is another superfluous name of Premna wui. We noticed that Li (2018) had reduced the superfluous name Premna cordiformis to a synonym of Premna wui.
The true identity of the Gymnosphaera gigantea (Cyatheaceae) in China

Authors: DONG SHI-YONG , HAQUE KAMRUL , RAHMAn MOHAMMAD SAYEDUR
Published: June 2020

The scaly tree fern widely accepted as Gymnosphaera gigantea in China is demonstrated to be a separate species, G. henryi. Our field observations show that G. henryi is a good species and is readily recognized by the combination of stipe bearing 2-rowed scales throughout, pinnae being sessile, and most or at least lower pinnae being opposite on rachis. However, G. gigantea is different in stipe without 2-rowed scales above the base and pinnae being more or less petiolate and mostly alternate on rachis. Gymnosphaera henryi is common in southern and southwestern China and Vietnam and is currently known also in Laos and Myanmar.
Begonia tadungensis (Begonia sect. Platycentrum), a new species from southern Vietnam

Authors: DO TRUONG VAN , LUU ANH NGOC DAM , DONG WEN-KE
Published: June 2020

We here describe and illustrate Begonia tadungensis (B. sect. Platycentrum), a new species from southern Vietnam. The new species is most similar to B. albopunctata in having broadly ovate leaves, three free styles, 4-loculed ovary, and berry-like fruits with a beaked apex, but differs mainly in having a glabrous abaxial leaf surface (not densely red pubescent), and fruits with gray puberlous hairs (not white papillose). It is also similar to B. pendens in its broadly ovate leaves and monoecious breeding system, but differs in having 6 tepals in the pistillate flowers (not 5) and 4-loculed ovaries (not 3-loculed). Information on ecology, conservation status, and a further comparison of characters with these two similar species is also provided.
Cryptothecia aleurodes (Arthoniaceae), a misunderstood species

Authors: BORGATO LUCA , ERTZ DAMIEN
Published: June 2020

Cryptothecia aleurodes was considered to be a widespread, rare tropical lichen having white ascigerous areas and a crustose whitish-grey thallus containing norstictic acid. A revision of its type specimen from Guadeloupe and the study of recent specimens from Martinique proved that the species has been misunderstood. In this paper, Cryptothecia aleurodes is shown to have a K– and C+ red thallus containing notably gyrophoric acid as major secondary metabolite but lacking norstictic acid. A detailed description and illustrations are provided. The species is known with certainty only from the Caribbean and has probably a Neotropical distribution. Previous reports of C. aleurodes from the Seychelles and Thailand are shown to be misidentifications and reports from India are considered dubious.
An overview of the African genera of Prodidominae spiders: descriptions and remarks (Araneae: Gnaphosidae)
Authors: RODRIGUES BRUNO V. B. , RHEIMS CRISTINA A.
Published: June 2020

A taxonomic revision of exclusively African genera of Prodidominae (Gnaphosidae), with the exception of Theuma, is provided. Austrodomus Lawrence, 1947 is revised. The type species A. zuluensis Lawrence, 1947 is redescribed, the male of A. scaber (Purcell, 1904) is described for the first time, and one new species, A. gamsberg sp. nov. (♂), is described from Namibia. Katumbea Cooke, 1964 is considered a junior synonym of Austrodomus and A. oxoniensis (Cooke, 1964) comb. nov. from Tanzania is redescribed. Eleleis Simon, 1893 is revised. The type species, E. crinita Simon, 1893, is redescribed and eight new species are described: E. limpopo sp. nov. (♂♀) from South Africa and Zambia, E. okavango sp. nov. (♂♀) from Botswana and Namibia, E. etosha sp. nov. (♂♀), E. himba sp. nov. (♂) and E. luderitz sp. nov. (♀) from Namibia, E. leleupi sp. nov. (♂) and E. haddadi sp. nov. (♀) from South Africa, and E. solitaria sp. nov. (♀) from Cape Verde. Purcelliana Cooke, 1964 is revised. The type species, P. problematica Cooke, 1964, is redescribed and three new species are described: P. kamaseb sp. nov. (♂♀) and P. khabus sp. nov. (♂♀) from Namibia, and P. cederbergensis sp. nov. (♂) from South Africa. Plutonodomus Cooke, 1964 is redescribed based solely on the type species, P. kungwensis Cooke, 1964. In addition, three new genera are described: Kikongo gen. nov., to include K. ruwenzori sp. nov. (♂♀) and K. buta sp. nov. (♂♀) from the Democratic Republic of the Congo (D.R. Congo), and K. rutshuru sp. nov. (♂♀) from D.R. Congo and Kenya; Kituba gen. nov., to include K. mayombensis sp. nov. (♂♀) and K. langalanga sp. nov. (♀) from D.R. Congo; and Yoruba gen. nov., to include Y. ibadanus sp. nov. (♂♀) from Nigeria and Y. toubensis sp. nov. (♂♀) from Ivory Coast. Distribution maps are provided for the species discussed in this study and an identification key is provided for all twelve genera of Prodidominae recorded in Africa.
Revision of Acrulia Thomson, 1858 and Dialycera Ganglbauer, 1895, with taxonomic notes on related genera and description of a new genus from the Caucasus (Coleoptera: Staphylinidae: Omaliinae: Omaliini)
Authors: SHAVRIN ALEXEY V. , ZANETTI ADRIANO
Published: June 2020

Two Palaearctic genera of the tribe Omaliini McLeay, 1825 are revised, redefined, and discussed: Acrulia Thomson, 1858, containing A. inflata (Gyllenhal, 1813), A. assingi Zanetti & Shavrin, sp.n. (Greece: Thessalia, Pelopónnisos), and A. akbesiana (Pic, 1898), revalidated from the synonymy with Dialycera aspera (Eppelsheim, 1889), and the genus Dialycera Ganglbauer, 1895, containing D. distincticornis (Baudi di Selve, 1870), D. aspera and D. minuta Luze, 1906. Taxonomic and faunistic notes for three species of the genus Acruliopsis Zerche, 2003 (A. denticollis (Sharp, 1889), A. tumidula (Mäklin, 1853) and A. ussuriensis Zerche, 2003) and four Palaearctic species of the genus Hapalaraea Thomson, 1858 (H. alutacea (Reitter, 1909), H. armeniaca (Székessy, 1939) comb.n. (from Acrulia), H. pygmaea (Paykull, 1800), and H. settei Zanetti, 1983) are provided. Hapalaraea alutacea and H. armeniaca are redescribed. Pseudodialycera Zanetti & Shavrin, gen.n., with the type species P. striatripennis (Aubé, 1850) comb.n. (from Dialycera) from the Caucasus, is described. A neotype for Acrulia akbesiana, and lectotypes for Omalium asperum Eppelsheim, 1889, O. inflatum Gyllenhal, 1813, and Phyllodrepa (Hapalaraea) alutacea Reitter, 1909 are designated. The following two synonymies are established: Acrulia akbesiana = Dialycera bimaculata Luze, 1906 syn.n., Hapalaraea pygmaea = Acrulia angusticollis Reitter, 1909 syn.n. The main morphological structures, including the genitalia and terminalia, are figured. Zoogeographic data are provided and mapped (except for Hapalaraea). Keys to the species of Acrulia and Dialycera, and a key to studied genera of Omaliini are provided. Several new records are reported: Acrulia inflata from Estonia, Greece, and Kazakhstan, Dialycera distincticornis from Montenegro and Greece, D. aspera from Greece and Jordan, and D. minuta from Armenia, Turkey, Lebanon and Jordan.