tbuckley/cabot-search huggingface dataset:
Abstract LB219: Methods to improve representation of racial and ethnic minorities in lung cancer screening programs: A systematic review
Authors: Tiffany J. Gilliard, Jaileene Perez-Morales, Matthew Schabath, Mary Katherine Haver
Journal: Cancer Research (2021)

Abstract Background: Most lung cancer screening trials to date and current screening guidelines overlook vulnerable populations with disproportionate lung cancer burden such as racial and ethnic minorities. Given the barriers, perceptions, and socioeconomic burden of these underserved populations, uptake of lung cancer screening has minimal. To develop and implement better methods of recruitment underserved populations, concerted efforts to understand the barriers and perceptions of these population are needed. Objective: Conduct a systematic review of methods for recruitment of racial and ethnic minorities into lung cancer screening trials or programs. Methods: We searched for studies that reported methods of recruitment and racial and ethnic minorities into lung cancer screening from 2010 to June 2020, using Ovid MEDLINE and Embase databases. Full-text screening and data extraction were completed independently by two reviewers and adjudication was performed by a third, independent reviewer. We compared referral rates of the recruitment modalities by racial/ethnic subgroups and by sex. Results: We identified 525 studies of which 25 were included in the systematic review corresponding to 291,329 patients. The most frequent methods of recruitment were referral, physical mail, community-based strategies, targeted strategies, phone, advertisement, and social media. Referral (n=7; 2,510 patients) was the most effective method of recruitment with response rates ranging from 31% to 97%. Direct mail (n=8 studies; 189,799 patients) was the second most extensively used recruitment method with response rates of 28% to 79%. Direct mail to Hispanic patients (2,995 total) for lung cancer screening programs was more effective than other methods of recruitment. Direct mail was more effective in recruiting African American patients (8,331 total) compared to referral (1,083 total). Conclusion: This review identified recruitment modalities that were more successful and less unsuccessful in recruiting racial and ethnic minorities into lung cancer screening trials and programs. This work highlights priorities and next steps required to improve recruitment of racial and ethnic minorities in lung cancer screening. There is a need to develop culturally relevant lung cancer screening interventions for Hispanics/Latino patients and to create targeted intervention for African American patients. Citation Format: Tiffany J. Gilliard, Jaileene Perez-Morales, Matthew Schabath, Mary Katherine Haver. Methods to improve representation of racial and ethnic minorities in lung cancer screening programs: A systematic review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB219.
Telemedicine in Surgery—Beyond a Pandemic Adaptation
Authors: Hassan M. K. Ghomrawi, Jane L. Holl, Fizan Abdullah
Journal: JAMA Surgery (2021)

Telemedicine in Surgery-Beyond a Pandemic AdaptationThe rapid transformation of the health care delivery system and surgical services across the US as a result of the COVID-19 pandemic was unprecedented.To limit COVID-19 exposure and transmission between patients and clinicians, millions of elective surgical procedures were suspended and necessity compelled surgeons to adopt telemedicine for preoperative, follow-up, and emergent surgical care visits.By summer 2020, surgical care gradually started returning to business as usual, but with the resurgence of COVID-19 cases in the fall and winter, suspension of elective surgery was reinstated in some states with surgical outpatient care continuing to be delivered by telemedicine.Substantive changes in regulations permitting telemedicine clearly facilitated the dramatic shift to telemedicine during the pandemic.Arguably, the most important of these regulations is that of the US Centers for Medicare & Medicaid Services (1135 Waivers) making reimbursement of in-person and telemedicine visits equal in March 2020. 1 Other third-party payers quickly followed.As a result, hospitals and surgical departments repositioned available technology to initiate widespread delivery of care by telemedicine.These institutions used primarily synchronous (eg, videoconference telemedicine visits) and asynchronous (eg, text messages, email, patient portal) telemedicine modalities. 2 The third modality, remote patient monitoring, which uses technology such as wearable devices to monitor patients outside conventional clinical settings, was least used.Approval of several effective COVID-19 vaccines and initiation of vaccination programs should, in time, mitigate the need to reduce in-person health care visits.While some proclaim that the pandemic finally surmounted long-standing resistance to the adoption and integration of major digital and technological advances into health care delivery, 1 recent national data suggest that the matter may be more nuanced.In a Commonwealth report, Mehrotra and colleagues 3 analyzed 50 million outpatient visits (up to October 1, 2020) and found a rebound of in-person, outpatient visits to pre-COVID-19 levels with a concomitant decline in telemedicine visits.In fact, in-person surgical visits were higher compared with the prepandemic period with telemedicine visits only accounting for 2% to 3% of all visits.This resurgence of in-person surgical care may signal that telemedicine may not be a satisfactory or sufficient replacement.While the COVID-19 pandemic highlighted the feasibility of using telemedicine to deliver some aspects of surgical care, the Commonwealth report 3 suggests that it may be viewed, by both patients and clinicians, as a temporary adaptation rather than a permanent substitute for in-person visits, even with expanded reimbursement.
Abstract 583: Analysis of solid pediatric tumor methylomes reveals a shared cancer recurrence signature in cell-free DNA
Authors: David N. Buckley, Ben Tew, Gerald Gooden, Timothy Triche, Bodour Salhia
Journal: Cancer Research (2021)

Abstract Cancer is the second most common cause of death in children aged 1-14 years in the United States, with approximately 11,000 new cases and 1200 deaths annually. Due in part to the rarity and diversity of childhood tumors, a non-invasive diagnostic to identify patients at high risk of recurrence does not exist for patients with pediatric solid cancer. Cell-free (cf)DNA is rapidly becoming the standard for non-invasive screening, diagnosis, treatment and monitoring of human tumors. In particular, cfDNA methylation detection has proven to be a robust platform for “liquid biopsies,” with several important advantages over simple somatic variant detection. Here we present a cfDNA methylation signature derived from a pan-methylome analysis of recurrent pediatric tumors. The methylomes spanned 34 tumor tissue samples, 13 patient-matched adjacent normal, and 16 patient-matched plasma samples from 27 individuals, representing 11 different pediatric tumor types, including 10 neuroblastomas, 4 osteosarcomas and 2 hepatoblastomas. In addition, 13 adjacent normal samples and 15 normal plasma samples were used as DNA methylation controls. These samples were obtained from the Pediatric Oncology Experimental Investigators' Consortium (POETIC) under informed consent. DNA methylation was analyzed for all samples by whole genome bisulfite sequencing (WGBS). Using consensus DNA methylation calling, we identified a set of 402 differentially methylated regions (DMR) in genomic DNA from tissue, with substantial enrichment of hypomethylated DMRs across a majority of samples. CpGs that were commonly hypomethylated were combined into consensus ‘hotspots.' In order to discriminate between tumor/normal samples in tissue, we applied supervised machine learning to train a classifier on these 402 features. Mean methylation across these 402 CpG hotspots was significantly (p &amp;lt; 0.01) lower in disease plasma compared to normal control plasma samples. We then tested the classifier on the 16 patient-matched cfDNA samples and achieved a classification accuracy of 95% and an area under the curve (AUC) of 0.935. In summary, we have identified a promising set of DNA methylation features also detected in cfDNA that can potentially be used for recurrence risk stratification and measurable minimal residual disease monitoring in solid pediatric tumors. Citation Format: David N. Buckley, Ben Tew, Gerald Gooden, Timothy Triche, Bodour Salhia. Analysis of solid pediatric tumor methylomes reveals a shared cancer recurrence signature in cell-free DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 583.
フランスにおける輸入された重症マラリアにおけるPlasmodium falciparum赤血球膜蛋白質1のドメインカセット4 8および13の優先的発現【Powered by NICT】
Authors: N Argy, G I Bertin, J Milet, V Hubert, J Clain, S Cojean, P Houze, N Tuikue-Ndam, E Kendjo, P Deloron, S Houze
Journal: Clinical Microbiology and Infection (2017)
Targeted therapy in advanced non-small cell lung cancer: current advances and future trends
Authors: Umair Majeed, Rami Manochakian, Yujie Zhao, Yanyan Lou
Journal: Journal of Hematology & Oncology (2021)

Abstract Lung cancer remains the leading cause of cancer-related mortality in both men and women in the US and worldwide. Non-small cell lung cancer is the most common variety accounting for 84% of the cases. For a subset of patients with actionable mutations, targeted therapy continues to provide durable responses. Advances in molecular and immunohistochemical techniques have made it possible to usher lung cancer into the era of personalized medicine, with the patient getting individualized treatment based on these markers. This review summarizes the recent advances in advanced NSCLC targeted therapy, focusing on first-in-human and early phase I/II clinical trials in patients with advanced disease. We have divided our discussion into different topics based on these agents' mechanisms of action. This article is aimed to be the most current review of available and upcoming targeted NSCLC treatment options. We will also summarize the currently available phase I/II clinical trial for NSCLC patients at the end of each section.
Increased doses of an anti-CD30 antibody, MDX-060, results in prolonged progression free survival in subjects with CD30 positive lymphoma.
Authors: Stephen Ansell, Steven Horwitz, Andreas Engert, Khuda Khan, Thomas Lin, Roger Strair, Albert Assad, Michael Yellin, Robert Graziano, Diann Blanset, Jason Tian, Zuoshun Zhang, Claire Barcellona, Peter Borchmann
Journal: Cancer Research (2008)

5525  MDX-060 is a human anti-CD30 IgG1kappa monoclonal antibody that inhibits the growth of CD30+ lymphoma cells. To determine the safety and efficacy of MDX-060 in patients with relapsed or refractory CD30+ lymphomas, MDX-060 was administered intravenously at doses of 0.1, 1, 5, 10 or 15 mg/kg weekly for 4 weeks in a phase I/II clinical trial. As previously reported, 72 patients were included in the study - 3 patients received 0.1mg/kg, 16 patients 1mg/kg, 20 patients 5mg/kg, 16 patients 10mg/kg and 17 patients received 15mg/kg. Treatment with MDX-060 was well tolerated with few side effects, however only 6 patients had a clinical response to therapy. Based on the premise that interference with CD30 signaling may result in the arrest of cell growth rather than lysis of the cell, we have now conducted a further analysis with longer follow up to assess whether higher doses of MDX-060 resulted in increased numbers of patients with stable disease and a longer progression free survival (PFS). When patients treated with doses of MDX-060 ≥10mg/kg (high dose group: n=33) were compared to patients who received doses of MDX-060
Abstract LB185: BBX and PLK1 feedback mechanisms regulate mitotic entry &amp; exit
Authors: Gaiyun Li, Maura L. Gillison
Journal: Cancer Research (2021)

Abstract Bobby Sox Homolog (BBX) is a highly conserved member of the high mobility group (HMG) box family of transcription factors, but its function remains largely unknown. We find human papillomavirus positive oropharyngeal squamous cell carcinomas (HPV-OPSCC) are enriched for BBX amplification and single nucleotide variants clustered within the BBX lysine rich domain. We therefore used the immortalized keratinocyte cell line HaCaT to elucidate BBX function. BBX is localized primarily in the nucleus. Cell synchronization at G1-S or G2-M shows BBX mRNA transcription and protein expression are highest at G1-S and rapidly decline at G2-M. Immunofluorescence (IF) shows high nuclear BBX expression during interphase and rapid reduction at mitosis (M). Induced overexpression of BBX decreases cellular proliferation, prolongs M phase, induces senescence, increases frequency of binucleated cells, and increases DNA damage as measured by γH2AX. Knockdown of BBX expression decreases cell proliferation, shortens M phase, and results in several mitotic defects, including lagging chromosomes, micronuclei, multi-polar spindles, and binucleated cells. Because effects of BBX dysregulation mirror those of Polo-like kinase-1 (PLK1), we investigated possible BBX-PLK1 interactions. BBX induction increases, whereas knockdown decreases, PLK1 mRNA and protein expression. BBX strongly activated transcription of the PLK1 promoter in a luciferase reporter assay. In contrast, PLK1 dramatically decreased BBX protein, but not mRNA, expression, and this effect was attenuated by a PLK1 T210 inactivating mutation and by a PLK1 small molecule inhibitor. We found a strong positive correlation between BBX and PLK1 mRNA expression in HNSCC tumors, but not in normal tissues. We conclude that BBX and PLK1 interact in a feedback mechanism to precisely regulate the G2-M transition. Future work will investigate interactions between BBX, HPV oncoproteins, and regulation of the cell cycle. Citation Format: Gaiyun Li, Maura L. Gillison. BBX and PLK1 feedback mechanisms regulate mitotic entry &amp; exit [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB185.
LITA-PA fistulaを利用したY composite graftによるOPCABの1例
Authors: 曽我欣治, 羽生道弥, 野本卓也, 新井善雄, 中野穣太, 松尾武彦, 甲斐正嗣, 梅原英太郎, 川東正英, 岡林均
Journal: Circulation (2007)
Proton pump inhibitors and risk of gastric cancer: population-based cohort study
Authors: Devin Abrahami, Emily Gibson McDonald, Mireille E Schnitzer, Alan N Barkun, Samy Suissa, Laurent Azoulay
Journal: Gut (2021)

To determine whether new users of proton pump inhibitors (PPIs) are at an increased risk of gastric cancer compared with new users of histamine-2 receptor antagonists (H2RAs).
Abstract 2954: Humanized CCR8 mouse model provides a translational tool for anti-human CCR8 antibody drug development
Authors: Linlin Wang, Chengzhang Shang, Jing Zhang, Yichao Chen, Leila Kokabee, Qingcong Lin
Journal: Cancer Research (2021)

Abstract CCR8 is reported as an important chemokine receptor expressed on intra-tumoral Tregs and plays a critical role in CCR8+Treg-mediated immunosuppression via inducing STAT3-dependent overexpression of FOXP3, CD39, IL-10, and granzyme B on Tregs with interaction of CCL1 (CCR8 ligand). CCR8 becomes a promising target in the anticancer drug development. Generation of humanized CCR8 mouse model can greatly improve translation and accelerate CCR8-related drug development. To evaluate the anti-tumor efficacy of human CCR8 blockade in tumor mouse models, Biocytogen has successfully generated a novel CCR8 humanized knock-in mouse strain to support anti-human CCR8 antibody drug development. In this mouse model, the full length of encoding sequences of mouse CCR8 gene were replaced by the full length of encoding sequences of human CCR8 (hCCR8) gene. CCR8 gene expression in WT and B-hCCR8 mice were tested by RT-PCR. Human CCR8 mRNA was detected in hCCR8 mice model but not in wild-type mice. Protein expression of human CCR8 in hCCR8 mice was evaluated by flow cytometer in a colon cancer cell line MC38 tumor bearing mouse model. The human CCR8 protein were successfully detected in tumor-infiltrating Tregs in B-hCCR8 mice bearing MC38 tumor, but not in Treg cells from spleen. An anti-tumor efficacy study showed significant tumor growth inhibition of hCCR8 antibodies in B-hCCR8 mice bearing MC38 tumors, suggesting that the B-hCCR8 mouse model is an effective tool for in vivo efficacy evaluation of therapeutic hCCR8 antibodies to support anti-human CCR8 antibody clinical development. Citation Format: Linlin Wang, Chengzhang Shang, Jing Zhang, Yichao Chen, Leila Kokabee, Qingcong Lin. Humanized CCR8 mouse model provides a translational tool for anti-human CCR8 antibody drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2954.
What part does ureteroscopy play in the diagnostic pathway of upper tract urothelial carcinoma? A two-year review in a high volume institution
Authors: R. Sehgal, S. Wong, Y. Abu-Ghanem, T. Birks, R. Kucheria, D. Allen, A. Goyal, P. Singh, L. Ajayi, G. Ellis
Journal: European Urology (2021)
Abstract 584: Circulating tumor cells as prognostic biomarkers in glioblastoma
Authors: Juliana Müller Bark, Arutha Kulasinghe, Paul Leo, Gunter Hartel, Majid E. Warkiani, Rosalind L. Jeffree, Benjamin Chua, Bryan W. Day, Chamindie Punyadeera
Journal: Cancer Research (2021)

Abstract Background: Glioblastoma (GBM) is the most common and aggressive type of tumor arising from the central nervous system. GBM remains an incurable disease despite current advancement in therapies, with survival rates of approximately 15 months. Recent literature has highlighted that GBM can release tumoral content which crosses the blood-brain barrier (BBB) and as a consequence can be detected in patients' blood, such as circulating tumor cells (CTCs). CTCs carry tumor information and have shown promise as prognostic and predictive biomarkers in other cancer types. Currently, the prognostic utility of CTCs in GBM is not well understood. Methods: Blood samples from GBM patients (n=18) attending a tertiary referral hospital were collected before and after surgery to investigate the prognostic role of CTCs. CTCs were isolated using spiral microfluidic technology and characterized using immunofluorescence for GFAP, cell surface vimentin and CD45, in addition to fluorescence in situ hybridization (FISH) to detect EGFR amplification. CTC counts of patients with poor outcomes (recurrence or death) versus patients with good outcomes (stable disease and no recurrence) were compared using a negative binomial distribution. Results: CTCs were found in 12 out of 18 patients (66.7%), 8/18 before surgery and 10/17 after surgery. CTC clusters were found in 2 patients. CTCs counts before surgery were significantly higher for patients with poor clinical outcome (p=0.0396). Conclusion: Our preliminary data support the use of this spiral technology to isolate CTCs. CTCs and CTC clusters can be used as prognostic biomarkers for managing GBM patients. Citation Format: Juliana Müller Bark, Arutha Kulasinghe, Paul Leo, Gunter Hartel, Majid E. Warkiani, Rosalind L. Jeffree, Benjamin Chua, Bryan W. Day, Chamindie Punyadeera. Circulating tumor cells as prognostic biomarkers in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 584.
Abstract 2827: Inactivating calcium-sensing receptor polymorphisms at rs1801725 are associated with increased risk of secondary malignancies
Authors: Heather K. Beasley, Ky'Era V. Actkins, Annika B. Faucon, Lea K. Davis, Amos M. Sakwe
Journal: Cancer Research (2021)

Abstract The dysregulation of systemic calcium homeostasis during malignancy is common in most patients with high-grade tumors. The associated comorbidity is known as cancer-induced hypercalcemia (CIH) which affects up to 30% of cases, in the absence of metastasis. In the course of breast cancer progression, the secretion of parathyroid hormone-related protein (PTHrP) by tumor cells and the associated destruction of bone tissues, leads to a progressive increase in systemic calcium or CIH. The increase in circulating Ca2+ is sensed by the calcium-sensing receptor (CaSR), which plays a significant role in maintaining Ca2+ homeostasis. More than 200 mutations and single nucleotide polymorphisms (SNPs) in the CaSR gene have been described, including the A986S CaSR at rs1801725 and Q1011E CaSR at rs1801726 SNPs with reduced sensitivity to Ca2+. Interestingly, high circulating Ca2+ is associated with aggressive breast tumors in premenopausal women and larger tumors in postmenopausal women; however, the contribution of the CaSR in breast cancer progression remains poorly understood. Unlike SNPs at rs1801726, up to 20% of breast cancer patients with SNPs at rs1801725 may be predisposed to higher circulating Ca2+ in the course of their disease. Since breast cancer frequently metastasizes to Ca2+ rich skeletal tissues, we hypothesize that the development of CIH and subsequent desensitization of the CaSR by sustained high Ca2+ is critical for both the adaptation of TNBC cells to CIH in Ca2+ rich microenvironments and TNBC progression. Our preliminary data reveal that the expression level and mutational status of the CaSR is cell type-specific, and that sustained high Ca2+ desensitizes the receptor, but promotes tumor cell growth and motility. In addition, our preliminary data show that the A986S SNP is associated with hypercalcemia, secondary malignancy of bone and respiratory organs, and deficiency of humoral immunity. This study provides novel insights into not only the adaptation of TNBC cells to high circulating Ca2+, but also suggests that mutations of the CaSR at rs1801725 are predictive of the likelihood for metastasis to lungs and bone. Citation Format: Heather K. Beasley, Ky'Era V. Actkins, Annika B. Faucon, Lea K. Davis, Amos M. Sakwe. Inactivating calcium-sensing receptor polymorphisms at rs1801725 are associated with increased risk of secondary malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2827.
Is flexible ureteroscopy and laser lithotripsy (FURLS) the new gold standard for paediatric lower pole stones: Outcomes from 2 large European tertiary paediatric endourology centres
Authors: L. Mosquera Seoane, A. Pietropaolo, Y. Quiroz Madarriaga, E. Llorens De Knecht, P. Jones, A. Bujons Tur, S. Griffin, B.K. Somani
Journal: European Urology (2021)