tbuckley/cabot-search huggingface dataset:
SIRPα-αCD123 fusion antibodies targeting CD123 in conjunction with CD47 blockade enhance the clearance of AML-initiating cells
Authors: Siret Tahk, Binje Vick, Björn Hiller, Saskia Schmitt, Anetta Marcinek, Enrico D. Perini, Alexandra Leutbecher, Christian Augsberger, Anna Reischer, Benjamin Tast, Andreas Humpe, Irmela Jeremias, Marion Subklewe, Nadja C. Fenn, Karl-Peter Hopfner
Journal: Journal of Hematology & Oncology (2021)

Acute myeloid leukaemia (AML) stem cells (LSCs) cause disease relapse. The CD47 "don't eat me signal" is upregulated on LSCs and contributes to immune evasion by inhibiting phagocytosis through interacting with myeloid-specific signal regulatory protein alpha (SIRPα). Activation of macrophages by blocking CD47 has been successful, but the ubiquitous expression of CD47 on healthy cells poses potential limitations for such therapies. In contrast, CD123 is a well-known LSC-specific surface marker utilized as a therapeutic target. Here, we report the development of SIRPα-αCD123 fusion antibodies that localize the disruption of CD47/SIRPα signalling to AML while specifically enhancing LSC clearance. SIRPα-αCD123 antibodies were generated by fusing the extracellular domain of SIRPα to an αCD123 antibody. The binding properties of the antibodies were analysed by flow cytometry and surface plasmon resonance. The functional characteristics of the fusion antibodies were determined by antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity assays using primary AML patient cells. Finally, an in vivo engraftment assay was utilized to assess LSC targeting. SIRPα-αCD123 fusion antibodies exhibited increased binding and preferential targeting of CD123+ CD47+ AML cells even in the presence of CD47+ healthy cells. Furthermore, SIRPα-αCD123 fusion antibodies confined disruption of the CD47-SIRPα axis locally to AML cells. In vitro experiments demonstrated that SIRPα-αCD123 antibodies greatly enhanced AML cell phagocytosis mediated by allogeneic and autologous macrophages. Moreover, SIRPα-αCD123 fusion antibodies efficiently targeted LSCs with in vivo engraftment potential. SIRPα-αCD123 antibodies combine local CD47 blockade with specific LSC targeting in a single molecule, minimize the risk of targeting healthy cells and efficiently eliminate AML LSCs. These results validate SIRPα-αCD123 antibodies as promising therapeutic interventions for AML.
Trends in Race and Ethnicity Among Matriculants to US Oncology Training Programs, 2015-2020
Authors: Jacob J. Lang, Rochell Issa, Conner Lombardi, Emilie Garcia, Oluchi C. Oke, Obi Ekwenna
Journal: JAMA Network Open (2021)

The demographics of practicing physicians in the US have not represented the diverse populations they serve, and there is no exception in oncology care.1,2 Recognizing the detrimental effects of these disparities on public health, oncology training programs have instilled benchmarks and initiatives to increase diversity among oncology physicians nationwide.3 However, data about representation in oncology specialties and the impact of these initiatives is lacking. This study aims to assess underrepresented minority (URM; ie, Black or African American individuals, Hispanic or Latino individuals, and Native American, American Indian, or Alaskan Native individuals) representation trends across training programs in oncology specialties from 2015 to 2020.
350P Molecular profiling of tumor tissue and tumor-derived cell lines in patients with glioblastoma
Authors: T. Nasedkina, V. Varachev, O. Susova, G. Krasnov, A. Poletaeva, A.A. Mitrofanov, D. Naskhletashvili, A. Bekyashev
Journal: Annals of Oncology (2021)
1718P Quality of life of patients with cancer and their family caregivers at the University of the Philippines – Philippine General Hospital Cancer Institute using the WHO Quality of Life-BREF Filipino
Authors: H.N. Tan, R.N. Velasco, L.I. Catedral, L.M. Leones, M.D. San Juan, C.A. Ngelangel, E. Calvo
Journal: Annals of Oncology (2021)
Immune-mediated attenuation of influenza illness after infection: opportunities and challenges
Authors: Manish M Patel, Ian A York, Arnold S Monto, Mark G Thompson, Alicia M Fry
Journal: The Lancet Microbe (2021)

Sterilising immunity that blocks infection for life, and thus prevents illness after infection, is the ultimate goal for vaccines. Neither influenza infection nor vaccination provide sterilising immunity. Mutations during influenza viral genome replication result in the emergence of viruses that evade immunity and cause reinfections. Waning of immunity also results in reinfections to homologous influenza viruses. However, immunity might limit the severity of disease after infection or vaccination (ie, immunoattenuation). We provide a comprehensive examination of experimental and observational peer reviewed evidence since 1933, when the first influenza virus was isolated, on whether immunity blocks subsequent infection or attenuates illness. Although an abundance of experimental evidence supports immunoattenuation, clinical evidence is rudimentary and conflicting. To the extent that immunoattenuation occurs, understanding the varied pathways to illness, pathogenesis, clinical manifestations, and correlates of attenuation can improve the design and evaluation of influenza vaccines. By elucidating the mechanisms of immunoattenuation and phenotypes of illness, we clarify ambiguities and identify unmet needs that, if addressed with priority, could strategically improve the design of vaccines for the prevention of influenza.
GALAD demonstrates high sensitivity for HCC surveillance in a cohort of patients with cirrhosis
Authors: Amit G. Singal, Nabihah Tayob, Anand Mehta, Jorge A. Marrero, Hashem El‐Serag, Qingchun Jin, Cristian Saenz de Viteri, Austin Fobar, Neehar D. Parikh
Journal: Hepatology (2021)

Abstract Background and Aims Most patients with HCC are diagnosed at a late stage, highlighting the need for more accurate surveillance tests. Although biomarkers for HCC early detection have promising data in Phase 2 case–control studies, evaluation in cohort studies is critical prior to adoption in practice. We leveraged a prospective cohort of patients with Child‐Pugh A or B cirrhosis who were followed until incident HCC, liver transplantation, death, or loss to follow‐up. We used a prospective specimen collection, retrospective, blinded evaluation design for biomarker evaluation of GALAD (gender × age × log alpha‐fetoprotein [AFP] × des‐gamma‐carboxy prothrombin), longitudinal GALAD, and the HCC Early Detection Screening (HES) algorithm—compared to AFP—using patient‐level sensitivity and screening‐level specificity. Approach and Results Of 397 patients with cirrhosis, 42 developed HCC (57.1% early stage) over a median of 2.0 years. Longitudinal GALAD had the highest c‐statistic for HCC detection (0.85; 95% CI, 0.77–0.92) compared to single–time point GALAD (0.79; 95% CI, 0.71–0.87), AFP (0.77; 95% CI, 0.69–0.85), and HES (0.76; 95% CI, 0.67–0.83). When specificity was fixed at 90%, the sensitivity for HCC of single–time point and longitudinal GALAD was 54.8% and 66.7%, respectively, compared to 40.5% for AFP. Sensitivity for HCC detection was higher when restricted to patients with biomarker assessment within 6 months prior to HCC diagnosis, with the highest sensitivities observed for single–time point GALAD (72.0%) and longitudinal GALAD (64.0%), respectively. Sensitivity of single–time point and longitudinal GALAD for early‐stage HCC was 53.8% and 69.2%, respectively. Conclusion GALAD demonstrated high sensitivity for HCC detection in a cohort of patients with cirrhosis. Validation of these results is warranted in large Phase 3 data sets.
Perforation of the capsule of Glisson by migration of a plastic biliary stent during a rendezvous and ERCP procedure
Authors: Paula Fernández-Alvarez, Juan Cintas-Catena, Victoria A. Jimenez-García, Francisco Bellido Muñoz, Rafael Romero-Castro, Pedro Hergueta-Delgado, Angel Caunedo-Alvarez
Journal: Endoscopy (2021)

Stent migration is a rare complication reported in 5 %–10 % of cases, with proximal migration being even more infrequent [1] [2]. Migration causing perforation of intrahepatic structures is exceptional, with only 14 cases reported [3]. We present a case of migrated plastic stent during a rendezvous and endoscopic retrograde cholangiopancreatography (ERCP) procedure, which led to perforation of Glisson’s capsule.
965MO GTB-3550 tri-specific killer engager safely activates and delivers IL-15 to NK cells, but not T-cells, in immune suppressed patients with advanced myeloid malignancies, a novel paradigm exportable to solid tumors expressing Her2 or B7H3
Authors: J.S. Miller, E.D. Warlick, R. Wangen, N. Zorko, P. Hinderlie, D. Lewis, D.A. Vallera, M. Felices
Journal: Annals of Oncology (2021)
131P Impact of body mass (BMI) and weight change after adjuvant treatment in patients (pts) with HER2-positive early breast cancer
Authors: M.A. Franzoi, S. Martel, D. Agbor-Tarh, M. Piccart, J. Bines, S. Loibl, S. Di Cosimo, I. Vaz-Luis, A. Di Meglio, L. Del Mastro, A. Gombos, C. Desmedt, G. Jerusalem, L. Reaby, T. Pienkowski, M. Lambertini, E. de Azambuja
Journal: Annals of Oncology (2021)
678P Cytoreductive nephrectomy (CN) for patients with metastatic sarcomatoid and/or rhabdoid (S/R) renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICI)
Authors: A.W. Hahn, P.V. Viscuse, A. Pieretti, A.J. Wiele, E. Jonasch, J. Gao, A.J. Zurita, A.Y. Shah, M.T. Campbell, P. Sharma, C.G. Wood, N.M. Tannir, J.A. Karam, P. Msaouel
Journal: Annals of Oncology (2021)
1682P Effects of a walking football program on muscle strength and balance of androgen deprived prostate cancer patients: The Prostata_Move trial
Authors: A.F. Baptista Capela, P. Antunes, A. Coelho, R. Amorim, S. Custodio, A. Amarelo, J. Silva, E. Vilela, A.J. Tavares, T. Costa, C. Garcia, J. Catarino, B. Travassos, R. Mendes, A. Joaquim, M. Teixeira, S. Viamonte, P. Figueiredo, J. Brito, A. Alves
Journal: Annals of Oncology (2021)
포스터전시 : 만성 B형 간염의 클레부딘 초치료 중 내성이외의 원인에 의한 엔테카비어 교체 후 치료 효과 (초)
Authors: In Do Song, Hyun Woong Lee, Hyung Joon Kim, Kwang Jin Kim, Kyu Hyun Yoon, Sang Pyo Han, Il Woon Park, Bong Ki Cha, Chang Hwan Choi, Jae Hyuk Do, Sae Kyung Chang
Journal: Clinical and Molecular Hepatology (2010)
1565MO Time-dependent improvement in the clinical outcomes from COVID-19 in cancer patients: An updated analysis of the OnCovid registry
Authors: D.J. Pinato, M. Patel, M. Lambertini, E. Colomba, F. Pommeret, M. Van Hemelrijick, A. Zambelli, T. Newsom-Davis, R. Salazar, A. Bertuzzi, G. Gaidano, G. Rizzo, G. Patel, E. Felip, A. Prat, J. Aguilar-Company, J. Tabernero, N. Diamantis, A. Gennari, A. Cortellini
Journal: Annals of Oncology (2021)
190P Clinical features and recurrence-free survival among young patients with breast cancer
Authors: A.S. Ferrigno, A. Aranda-Gutierrez, A. Becerril-Gaitan, B.F. Vaca-Cartagena, F.A. Gonzalez-Mondellini, M.A. Acosta-Sandoval, M. Roman-Zamudio, M.I. Torres-Leal, C.A. Treviño-Alanis, H.M. Diaz-Perez, R. Ortiz-López, S. Cardona, C. Villarreal-Garza
Journal: Annals of Oncology (2021)
Chronic unilateral nasal obstruction
Authors: Qingwu Wu, Qintai Yang
Journal: BMJ (2021)

A woman in her early 20s presented to the otorhinolaryngology clinic with a 10 month history of progressively worsening left sided nasal obstruction (“stuffy nose”) and rhinorrhoea. No seasonal pattern was detected. The patient’s right nostril was free of symptoms. She reported no bloodstained nasal discharge, headache, or olfactory dysfunction.

Anterior rhinoscopy showed a pale and translucent polypoid mass, without macroscopic surface ulceration, in the left nasal cavity. Computed tomography of the sinuses (fig 1) showed a dumbbell-shaped polyp with extension in the left sinonasal cavity.



Fig 1 
(A) Computed tomography (CT) coronal segment showing a polyp arising from the left maxillary sinus and extending through a widened maxillary sinus ostium into the nasal cavity. …
959O Gavocabtagene autoleucel (gavo-cel, TC-210) dose escalation in refractory mesothelin-expressing solid tumors
Authors: D.S. Hong, S.L. SciMentum, J. Tanyi, L. MacMullen, L. Jalbert, V.P. Muzithras, K. Zikaras, L. Cao, R.E. O’Cearbhaill, A. Quintás-Cardama, R. Hassan
Journal: Annals of Oncology (2021)
Down-regulation of farnesoid X receptor in human colorectal and hepatic cancers.
Authors: Ann Thomas, Manimaran Rengasamy, Bo Kong, John Robertson, Vadivel Ganapathy, Grace Guo
Journal: Cancer Research (2008)

4088  Bile acids are potential tumor promoting agents. Epidemiological studies suggest that secretion of bile acids is increased after consumption of a high-fat diet, which is a significant risk factor identified for colon cancer and non-alcoholic fatty liver disease/non-alcoholic steatohepatitis-derived liver cancer. Bile acids are identified as endogenous ligands for the farnesoid X receptor (FXR), a ligand-activated transcription factor and member of the nuclear receptor superfamily. FXR is essential for maintaining bile-acid homeostasis by regulating bile-acid synthesis and transport. Previous results from our and other laboratories demonstrated that FXR knockout mice are more susceptible to development of colorectal adenocarcinomas and hepatocarcinomas, indicating that FXR plays a suppressive role in enterohepatic tumor formation. However, the association of FXR with human colon and liver cancers has not been elucidated. The purpose of this study is to determine whether FXR functions to suppress the formation of human colorectal or liver tumors. In the current study, the expression and function of FXR was determined in normal and cancerous human colon and liver tissues. The levels of FXR mRNA were markedly reduced in the colorectal adenocarcinomas which did not correlate with the stage and differentiation of the tumors or the age and gender of the patients. In contrast, the levels of FXR mRNA were markedly reduced in the hepatomas, which are inversely correlated with the progression/stage of tumors. Furthermore, the expression of FXR target genes was reduced in both colon and liver cancers, indicating that the loss of FXR disrupts regulation of bile-acid homeostasis. In summary, the expression and function of the bile-acid nuclear receptor, FXR, was down-regulated in colorectal and hepatic cancers, indicating that FXR may play a suppressive role for enterohepatic tumor development.
Lenalidomide in combination with R-CHOP produces high response rates and progression-free survival in new, untreated diffuse large B-cell lymphoma transformed from follicular lymphoma: results from the Phase 2 MC078E study
Authors: Sanjal H. Desai, Betsy LaPlant, William R. Macon, Rebecca L. King, Yucai Wang, David J. Inwards, Ivana Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, Thomas E. Witzig, Grzegorz S. Nowakowski
Journal: Blood Cancer Journal (2021)

Diffuse large B-cell lymphoma (DLBCL), either concurrent with or transformed from follicular lymphoma (FL) is often excluded from clinical trials. Lenalidomide has response rates of 45% in relapsed transformed DLBCL. Herein we present an analysis of MC078E, a phase II clinical trial testing lenalidomide plus R-CHOP (R2CHOP) for patients with untreated transformed/concurrent DLBCL (NCT00670358). Adult patients with transformed or concurrent DLBCL were included. Patients received six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) with lenalidomide 25 mg days 1-10 of each cycle. The primary outcome was progression-free survival (PFS) at 24 months. Secondary outcomes were response rates, event-free survival (EFS), and overall survival (OS). Thirty-nine patients were accrued from August 5, 2013 to July 28, 2020 and 33 were eligible by central pathology review. The median age was 64 (24-80) years, 18 (54%) were male, 25 (76%) were concurrent and 8 (24%) were transformed DLBCL. The PFS, EFS, and OS rates at 24 months were 84.4% (CI95: 67.2-94.7%), 84.5% (CI95: 72.9-98%), and 97.0% (CI95: 91.3-100%), respectively. R2CHOP is effective in concurrent and transformed DLBCL. The study supports the inclusion of anthracycline-naive transformed and concurrent DLBCL in future clinical trials of novel immunomodulatory analogues.
1590P Treatment outcomes and antibody immunity to SARS-CoV-2 in patients with hematological malignancies
Authors: K. Zakurdaeva, O.A. Gavrilina, A.N. Vasileva, S.K. Dubov, V.S. Dubov, V.I. Vorobyev, L.S. Butaev, L.V. Gavrilova, I.Y. Toropova, M. Popova, A. Siniaev, K. Kaplanov, A.A. Petrenko, O.I. Ochirova, E.Y. Chelysheva, Y.V. Sveshnikova, V. Shuvaev, M.E. Grishunina, Y.A. Chabaeva, V.G. Savchenko
Journal: Annals of Oncology (2021)
1028TiP ARC-12: Phase I/Ib dose escalation and dose expansion study to evaluate the safety and tolerability of AB308 + zimberelimab (AB122) in advanced malignancies
Authors: J.A. Call, M.A. Mckean, P. Foster, C. Trudeau, M. Scharville, A. El-Baghdady, A. Patnaik
Journal: Annals of Oncology (2021)
1177P Real-world treatment patterns and outcomes in stage III non-small cell lung cancer (NSCLC): Middle East and Africa (MEA)-KINDLE study
Authors: A.R. Jazieh, E. Kaytan Saglam, H.C. Önal, Y. Abdelkader, R. Gaafar, E. Dawoud, M. Nassar, D. Alshorbagy, H. El Ashry, M. Alsayed
Journal: Annals of Oncology (2021)
A Young Man With Wide Complex Tachycardia—The Devil Is in the Details
Authors: Shivank Gupta, Ashutosh Yadav, Anunay Gupta
Journal: JAMA Internal Medicine (2021)

This case report describes a man in his 20s who presented to the emergency department with intermittent palpitations for 2 days and no history of chest pain, dyspnea, congestion, or fever. What is your diagnosis?
1397P Prognostic impact of infectious complications: Exploratory analysis of JCOG0501 phase III trial
Authors: M. Hayashi, J. Mizusawa, S. Hato, Y. Iwasaki, M. Sasako, Y. Kawachi, H. Iishi, Y. Choda, N. Boku, T. Yoshikawa, M. Terashima
Journal: Annals of Oncology (2021)
Examining the relationships between early childhood experiences and adolescent and young adult health status in a resource-limited population: A cohort study
Authors: Zeba A. Rasmussen, Wasiat H. Shah, Chelsea L. Hansen, Syed Iqbal Azam, Ejaz Hussain, Barbara A. Schaefer, Nicole Zhong, Alexandra F. Jamison, Khalil Ahmed, Benjamin J. J. McCormick
Journal: PLoS Medicine (2021)

Background Adolescence is a critical point in the realization of human capital, as health and educational decisions with long-term impacts are made. We examined the role of early childhood experiences on health, cognitive abilities, and educational outcomes of adolescents followed up from a longitudinal cohort study in Pakistan, hypothesizing that early childhood experiences reflecting poverty would manifest in reduced health and development in adolescence. Methods and findings Adolescents/young adults previously followed as children aged under 5 years were interviewed. Childhood data were available on diarrhea, pneumonia, and parental/household characteristics. New data were collected on health, anthropometry, education, employment, and languages spoken; nonverbal reasoning was assessed. A multivariable Bayesian network was constructed to explore structural relationships between variables. Of 1,868 children originally enrolled, 1,463 (78.3%) were interviewed as adolescents (range 16.0–29.3 years, mean age 22.6 years); 945 (65%) lived in Oshikhandass. While 1,031 (70.5%) of their mothers and 440 (30.1%) of their fathers had received no formal education, adolescents reported a mean of 11.1 years of education. Childhood diarrhea (calculated as episodes/child-year) had no association with nonverbal reasoning score (an arc was supported in just 4.6% of bootstrap samples), health measures (with BMI, 1% of bootstrap samples; systolic and diastolic blood pressure, 0.1% and 1.6% of bootstrap samples, respectively), education (0.7% of bootstrap samples), or employment (0% of bootstrap samples). Relationships were found between nonverbal reasoning and adolescent height (arc supported in 63% of bootstrap samples), age (84%), educational attainment (100%), and speaking English (100%); speaking English was linked to the childhood home environment, mediated through maternal education and primary language. Speaking English ( n = 390, 26.7% of adolescents) was associated with education (100% of bootstrap samples), self-reported child health (82%), current location (85%) and variables describing childhood socioeconomic status. The main limitations of this study were the lack of parental data to characterize the home setting (including parental mental and physical health, and female empowerment) and reliance on self-reporting of health status. Conclusions In this population, investments in education, especially for females, are associated with an increase in human capital. Against the backdrop of substantial societal change, with the exception of a small and indirect association between childhood malnutrition and cognitive scores, educational opportunities and cultural language groups have stronger associations with aspects of human capital than childhood morbidity.
1195P Brigatinib (BRG) vs crizotinib (CRZ) in ALK TKI–naive ALK+ NSCLC: Final results from ALTA-1L
Authors: S. Popat, H.R. Kim, M-J. Ahn, J.C. Yang, J-Y. Han, M.J. Hochmair, K.H. Lee, A. Delmonte, M.R. Garcia Campelo, D-W. Kim, F. Griesinger, E. Felip, R. Califano, A. Spira, S.N. Gettinger, M. Tiseo, H.M. Lin, Y. Liu, F. Vranceanu, D.R. Camidge
Journal: Annals of Oncology (2021)
486P Bioavailability and activity of oncolytic virus TG6002 after intravenous administration in patients with advanced gastrointestinal carcinomas
Authors: P.A. Cassier, K. Bendjama, V. Moreno Garcia, B. Doger De Speville Uribe, E. Calvo, M.J. de Miguel, C. Jungels, P. Erbs, D. Carpentier, A. Sadoun
Journal: Annals of Oncology (2021)
1264P Early circulating tumour DNA (ctDNA) dynamics for predicting and monitoring response to immunotherapy (IO) vs chemotherapy (CT) in patients with 1L metastatic (m) NSCLC: Analyses from the phase III MYSTIC trial
Authors: S. Peters, N.A. Rizvi, M. Kuziora, Z. Lai, Y. Shrestha, A. Dey, J.C. Barrett, U. Scheuring, L. Poole, C. Abbosh, R. Raja, M.D. Hellmann
Journal: Annals of Oncology (2021)
Dysregulated APOBEC3G causes DNA damage and promotes genomic instability in multiple myeloma
Authors: Srikanth Talluri, Mehmet K. Samur, Leutz Buon, Subodh Kumar, Lakshmi B. Potluri, Jialan Shi, Rao H. Prabhala, Masood A. Shammas, Nikhil C. Munshi
Journal: Blood Cancer Journal (2021)

Abstract Multiple myeloma (MM) is a heterogeneous disease characterized by significant genomic instability. Recently, a causal role for the AID/APOBEC deaminases in inducing somatic mutations in myeloma has been reported. We have identified APOBEC/AID as a prominent mutational signature at diagnosis with further increase at relapse in MM. In this study, we identified upregulation of several members of APOBEC3 family (A3A, A3B, A3C, and A3G) with A3G, as one of the most expressed APOBECs. We investigated the role of APOBEC3G in MM and observed that A3G expression and APOBEC deaminase activity is elevated in myeloma cell lines and patient samples. Loss-of and gain-of function studies demonstrated that APOBEC3G significantly contributes to increase in DNA damage (abasic sites and DNA breaks) in MM cells. Evaluation of the impact on genome stability, using SNP arrays and whole genome sequencing, indicated that elevated APOBEC3G contributes to ongoing acquisition of both the copy number and mutational changes in MM cells over time. Elevated APOBEC3G also contributed to increased homologous recombination activity, a mechanism that can utilize increased DNA breaks to mediate genomic rearrangements in cancer cells. These data identify APOBEC3G as a novel gene impacting genomic evolution and underlying mechanisms in MM.