tbuckley/cabot-search huggingface dataset:
Circulating immunoreactive Interleukin-6 (IL-6) in cystic fibrosis
Authors: L. S. Nixon, B. Yung, S. C. Bell, J. S. Elborn, D. J. Shale
Journal: Thorax (1996)

Cytokine networks are important in infectious lung conditions. Previous studies have demonstrated circulating levels of neutrophil elastase-α-anti-proteinase complex (NEAPC) and C-reactive protein (CRP) as markers of inflammatory activity in cystic fibrosis (CF). In this study Interleukin-6 (IL-6) and Tumour necrosis-α (TNFα) levels were compared to NEAPC and CRP. Twelve patients with CF and chronically infected with P.aeruginosa were studied at the start of an exacerbation, after antibiotic treatment, and while clinically stable; 12 healthy non-CF subjects were matched at each time point. Venous blood was obtained for serum (IL-6 and CRP) and EDTA plasma (NEAPC and TNFα). Aliquots were stored at -70°C until assayed by ELISA. Lung function was determined at the same time. IL-6, NEAPC, CRP and peripheral blood absolute neutrophil count were all reduced (p<0.01) after antibiotic treatment. Levels of all these were greater in the stable group than at the end of an exacerbation; IL-6 (p=0.007) and CRP (p=0.01). IL-6 correlated (r=0.836;p<0.0001) with CRP, and both were significantly greater than in controls (p<0.001) at all study times. FEV and FVC improved with antibiotic treatment (p<0.01) but remained less than control values at all time points. IL-6 was related to other inflammatory markers, although the results for TNFα were less clear. CRP probably represents a down-stream indicator of IL-6, and therefore IL-6 may be an earlier indicator of inflammatory activity. The separation between patients and healthy subjects, the marked drop of IL-6 following antibiotic treatment and its close correlation with CRP supports the use of IL-6 as a circulating marker of inflammation in CF.
Correlation of NFE2L2 mutation with higher tumor mutation burden (TMB), microsatellite instability (MSI) and PD-L1 expression in 3,716 cases of Chinese pan-cancer.
Authors: Bin Wu, Aijun Li, Keji Chen, Lin Chen, Qin Zhang, Qianqian Duan, Mingzhe Xiao, Mengmeng Li
Journal: Journal of Clinical Oncology (2021)

e16211 Background: Nuclear factor E2-related factor-2 (NFE2L2) gene encodes a transcription factor which is a member of basic leucine zipper (bZIP) proteins family. Overexpression of NFE2L2 lead to cell proliferation and promoted tumor metastasis. Previous report indicated that NFE2L2 mutation (NFE2L2-MT) was an independent poor prognostic factor in esophageal squamous cell carcinoma (ESCC). However, the correlation between NFE2L2 mutation and pan-cancer types of TMB, MSI, and PD-L1 expression is unclear. Methods: TMB analysis was performed in 3,716 Chinese pan-cancer patients who underwent NGS sequencing using a 539 gene panel. The TMB calculation included synonymous and nonsynonymous mutations and InDels. MSI analysis was performed in 3,110 patients. MSI-H was defined as above 10% positive of the 195 tested microsatellites sites. The PD-L1 expression analysis was performed in 3,415 patients with immunohistochemistry staining (IHC) by antibody SP263. PD-L1 positive was defined as greater than or equal to 1%. The statistical correlation was investigated using Chi-square analysis. TMB value was compared using Wilcoxon Rank Sum test. We used TCGA public database to verify the result. Results: The mutation frequency of NFE2L2 mutation was 2.66% (99/3716). The TOP 5 cancer types were liver cancer 3.53% (14/397), lung cancer 2.97% (42/1416), colorectal cancer 2.02% (7/347), gastric cancer 1.36% (3/221), soft tissue sarcoma 0.53% (1/189). NFE2L2-MT had a significant correlation with higher TMB (p = 2.2e-16), compared with NFE2L2 wild-type (NFE2L2-WT). Among 3110 samples with MSI status, the MSI-H percentage of NFE2L2-MT and NFE2L2-WT were 8.60% (8/93) and 1.33% (40/3017), respectively (p = 1.29e-7). In 3,415 patients with PD-L1 protein expression information, the PD-L1 positive percentage of NFE2L2-MT and NFE2L2-WT were 51.52% (51/99) and 61.9% (1,268/2,048), respectively. NFE2L2-WT has higher PD-L1 positive percentage than NFE2L2-MT (p = 0.01). NFE2L2-MT was significantly correlated with higher TMB and MSI when we used TCGA data to verify, p&lt;0.0001. However, the survival analysis of 1661 MSKCC immunotherapy cohort showed that the median OS of NFE2L2-MT vs NFE2L2-WT was 21 months vs 18 months (p=0.858), but the difference was not significant. Conclusions: NFE2L2 mutation has a very significant correlation with higher TMB and MSI, but not related to PD-L1 expression. However, whether NFE2L2-MT is related to the efficacy of immunotherapy was still unclear and more clinical data were needed.
The cognitive load of inpatient consults: A convergent parallel mixed methods study using the consult cognitive load instrument.
Authors: Sam Brondfield, Kewchang Lee, Patricia O'Sullivan
Journal: Journal of Clinical Oncology (2021)

11027 Background: Consultation is crucial for inpatient care and a primary responsibility of fellows. Understanding the cognitive load associated with the complex skill of consultation would enhance fellow learning. The authors aimed to determine themes describing the fellow experience during consults, align these themes with Consult Cognitive Load (CCL) scores, and identify strategies to manage cognitive load. Methods: The authors studied 16 fellows using mixed methods. Fellows who accepted an invitation completed a consult followed by the CCL, a measure of cognitive load during consults, and an interview. Three authors conducted a thematic analysis. Member checks and triangulation with fellows supported theme trustworthiness. Subsequently, three authors rated the extent and cognitive demand of each theme expressed in each transcript. The authors measured interrater reliability and used Spearman correlation to describe the association of these ratings with CCL scores. The authors examined themes to identify strategies that educators might use. Results: Analysis revealed four themes: “nature and scope,” which conceptually aligned with intrinsic cognitive load (IL); “leveraging resources,” which had elements of both IL and extraneous cognitive load (EL); “extraneous factors,” which aligned with EL; and “drivers,” which aligned with germane cognitive load (GL). Interrater reliability for extent and demand ratings ranged from 0.57 to 0.79. The correlation between “nature and scope” and IL was 0.37, “extraneous factors” and EL 0.71, and “drivers” and GL 0.32. “Leveraging resources” did not correlate with IL (0.06) or EL (-0.09). Potential strategies based on themes included offering level-appropriate assistance to match IL, focusing the fellow’s attention to reduce EL, and providing succinct teaching to promote GL. Conclusions: This study provided deep insight into the fellow consult experience and suggested trustworthy strategies that educators can use to design and guide consult learning. The theme “leveraging resources” merits further exploration.
Abstract NT-095: ERADICATION OF CHEMORESISTANT METASTATIC OVARIAN CANCER WITH IMMUNOTARGETED EPIGENOMIC NANOSURGERY (IEN)
Authors: John N. Giannios
Journal: Clinical Cancer Research (2019)

Abstract INTRODUCTION: Resistance to conventional chemotherapy such as cisplatin, and radiotherapy in ovarian cancer may be caused by deregulated oncogenic miRNA-221/222 inhibiting induction of apoptosis. METHODS: Chemoradioresistant cells overexpressing EphA2 were obtained for developing an ovarian metastatic cancer model, which was treated with anti-EphA2 MAbs immunotargeted pegylated nanosomes with encapsulated paired guide-RNAs targeting 3' and 5' of the precursor microRNA 221/222. RESULTS: Post-treatment, the paired guide-RNAs caused deletions in the targeted pre-microRNA 221/222 genomic-sequences removing the stem-loop hairpins after blockade of RNase-III Drosha and DGCR8 (microprocessor-complex), subsequent transport by exportin-5/RanGTP and cleavage by Dicer inhibiting miRNA221/222 biogenesis, and miRNP circumventing their incorporation in RISC, and subsequent mRNA cleavage of coding genes regulating according to NGS the PTEN, GJA1, SEMA3B, TIMP3, PTPRM, CDKN1C, MGMT, CDKN1B, PUMA, connexin-43 (CX-43), c-Jun, MMP, NF-kB, PI3K, p27/Kip1, PTPμ, NIAP, ICAM-1, STAT1, STAT2, STAT3/Akt, CDK4, CDKN1C/p57, p53, and p57 inhibiting metastatic ovarian cancer cell proliferation, chemo/radioresistance, migration, angiogenesis, invasion, metastasis and maintenance of MET expressing ovarian metastatic cancer stem cells, while inducing cytotoxic immune responses (CTLs), and D2 irreversible stage of apoptosis or programmed cell death type-I leading to a bystander killing effect (BKE) due to phagocytosis of adjacent tumor cells according to transmission electron micrographs. CONCLUSION: Immunotargeted epigenomic nanosurgery may eradicate metastatic ovarian cancer after inhibition of oncogenic miRNA 221/222 expression, and downstream signaling pathways involving interactions with coding RNA genes leading to apoptosis or PCD type I and BKE after the circumvention of chemo/radioresistant mechanisms. Citation Format: John N. Giannios. ERADICATION OF CHEMORESISTANT METASTATIC OVARIAN CANCER WITH IMMUNOTARGETED EPIGENOMIC NANOSURGERY (IEN) [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-095.
Prevalence and risk factors of burnout among female oncology professionals from the Middle East and North Africa (MENA).
Authors: Atlal Abusanad, Assia Bensalem, Emad Shash, Layth Y.I. Mula-Hussain, Zineb Benbrahim, Sami Ahmad Khatib, Nafisa Abdelhafeiz, Jawaher Ansari, Hoda Jradi, Khaled Alkattan, Abdul-Rahman Jazieh
Journal: Journal of Clinical Oncology (2021)

11016 Background: Burnout (BO) is a recognized challenge among oncology workforce. It affects both genders with a higher frequency among women. This study examined the factors contributing to the development of burnout among women in oncology from the Middle East and North Africa (MENA). Methods: An online cross-sectional survey was distributed to oncology professionals from different countries in the MENA region. The validated Maslach Burnout Inventory (MBI) of emotional exhaustion (EE), Depersonalization (DE), and Personal Achievement (PA) plus questions about demography/work-related factors and attitudes toward oncology were included. Data were analyzed to measure BO prevalence and related factors. Results: Between February 10 and March 15, 2020, 545 responses were submitted by female professionals. The responses pre-dated the COVID-19 pandemic emergence in the region. BO prevalence was 71% among female professionals. Women aged &lt; 44 years represented 85% of the cohort. Sixty-two percent were married, 52% with children and one-third practiced a hobby. Two-thirds worked in medical oncology, worked for &lt; 10 years and 35% worked in academia. The majority (73%) spent &gt; 25% on administrative work daily. Nearly half of the respondents (49%) expressed a recurring thought of quitting oncology and 70% had no burnout support or education. Inability to deliver optimal care was reported as distressing for career development in 82%. Factors significantly influencing the BO risk are listed in Table. Marital status, having children, academia and years in practice did not impact the risk of BO among female oncologists form MENA. Conclusions: High BO prevalence was reported among female oncology professionals from MENA. The majority of women oncology workforce were young and early- to mid-career in this cohort. Younger age, practicing in North African countries, high administrative load and the recurring thought of quitting were associated with increased risk of burnout. Whereas, practicing a hobby and enjoying oncology communication decreased the BO risk. Burnout support and education specifically for women in oncology is needed.[Table: see text]
A phase II study of anlotinib in the first-line treatment of locally advanced or metastatic soft tissue sarcoma.
Authors: Xin Huang, Zhaoming Ye, Tao Li, Yongzhong Wei, Shoufeng Wang, Yunxia Liu, Jia Chen
Journal: Journal of Clinical Oncology (2021)

e23531 Background: Standard treatment for patients with unresectable locally advanced or metastatic soft-tissue sarcoma is chemotherapy based on anthracyclines, while the tolerance of chemotherapy is limited. We assessed if anlotinib, a multitarget tyrosine kinase inhibitor, is efficacy and safety for the first-line treatment of these patients. Methods: This is an open-label, single-arm, multicenter, phase II clinical trial (NCT03792542) including 44 planned subjects. Eligible patients were aged 18-70 years old, diagnosed with locally advanced or metastatic soft-tissue sarcoma and had at least one measurable lesion according to RECIST 1.1. Other inclusion criteria included ECOG PS 0̃2, chemotherapy and anti-angiogenesis treatment naïve. Patients were administrated 12mg anlotinib once daily for 14 days every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Safety assessment was done in patients who received at least one dose of anlotinib. Here we report the results of a planned interim analysis. Results: From April 2019 to December 2020, 29 patients (16 males and 13 females) were enrolled from 7 hospitals in China. The median age is 57 (range 23-69). Pathological types included liposarcoma (n = 8), undifferentiated pleomorphic sarcoma (n = 5), fibrosarcoma (n = 5), synovial sarcoma (n = 4), and others (n = 7). At the data cutoff date on December 31, 2020, the median duration of treatment was 5.3 months, and the median PFS was not reached. 26 patients were eligible for the evaluation of tumor response.1 achieved partial response (PR) and the objective response rate (ORR) was 3.85% (1/26). 24 had stale disease (SD) and the disease control rate (DCR) was 96.2% (25/26). The clinical benefit rate (CBR), defined as the proportion of patients who achieved durable disease control (CR/PR/SD) more than 4 and 6 months, were 65.4% (17/26) and 38.5% (10/26) respectively. Most adverse events (AE) were grade 1 or 2. The most common grade 3 AE was hypertension (17.2%). No grade 4 AEs or treatment related death occurred in this study through the last follow-up. Conclusions: This interim analysis showed anlotinib of promising efficacy and favorable tolerance in the first-line treatment of locally advanced or metastatic soft- tissue sarcoma. Clinical trial information: NCT03792542.
Gene fusions in glioblastoma: Results of Gliocat project.
Authors: Ainhoa Hernandez Gonzalez, Anna Esteve-Codina, Cristina Carrato, Ana Munoz, Estela Pineda, Oscar Gallego Rubio, Oriol Arpi, Marta Gut, Maria Martinez Garcia, Raquel Lopez, Carlos Mesia, Sonia DEL Barco Berron, Carolina Sanz, Sun Chen, Marta Domenech, Francesc Alameda, Carmen Balana
Journal: Journal of Clinical Oncology (2021)

2042 Background: Malignant gliomas are heterogeneous diseases in genetic basis. The development of sequencing techniques, such as RNA-Sequencing, has identified many gene rearrangements encoding novel oncogenic fusions. Gene fusion discovery can potentially lead to the development of novel treatments, however studies of gene fusions in glioma remain limited. Methods: The GLIOCAT project studied 139 patient samples of newly diagnosed glioblastoma who had received the standard first-line treatment from 2004 to 2015, to identify gene fusion events from glioblastoma transcriptome data (RNA-Seq). The molecular subtype could be studied in 124 cases. RNA-Seq reads were mapped against the reference human genome with STAR-fusion version 0.7.0, specifically, with FusionInspector validate ( http://star-fusion.github.io ). Two other platforms, FusionHub ( https://fusionhub.persistent.co.in ) and Oncofuse ( www.unav.es/genetica/oncofuse.html ), were applied to eliminate false positives or previously described in healthy tissue and to predict of the oncogenic potential each fusion. Results: A total of61 patients showed 103 different fusions, a median of two fusions by sample. The majority of gene fusions were intrachromosomal and most frequently implied chromosome was 12 followed by 7. In addition, fusions were more common in patients with MGMT promoter methylation, TCGA classical subtype and 18 IGS subtype. There were no differences in age, sex, type of surgery or long survivors ( &gt; 30 months). Ten fusions were already described in cancer, including three in gliomas (FRS2-KIF5A, EGFR-SEPT14 and FGFR3-TACC3). From the detected fusions, 22 of them included an oncogene or protooncogene. Conclusions: In our study, we report the landscape of gene fusions from a large data set of glioblastomas analyzed by RNA-seq. The majority of the fusions were private fusions. A minority of these recur in a low frequency but as many as a quarter of them included an oncogene or protooncogene. RNA-seq of GBM patient samples it is an important tool for the identification of patient-specific fusions that could drive personalized therapy. Furtherless, we will plan to validate this gene fusions.
Heart failure with preserved ejection fraction and <scp>COVID</scp>‐19: which comes first, the chicken or the egg? Letter regarding the article ‘Heart failure with preserved ejection fraction according to the <scp>HFA‐PEFF</scp> score in <scp>COVID</scp>‐19 patients: clinical correlates and echocardiographic findings’
Authors: Claudia Baratto, Sergio Caravita, Gianfranco Parati
Journal: European Journal of Heart Failure (2021)
Chromosome 6 Loss-of-Heterozygosity in Pre-Transplant Blood Samples of Patients with Severe Aplastic Anemia Is Associated with Lower Risk of Acute Graft- Versus -Host Disease
Authors: Shahinaz M Gadalla, Weiyin Zhou, Tao Wang, Yoshitaka Zaimoku, Shinji Nakao, Laurie Burdette, Amanda Willis, Medhat Askar, Michael Haagenson, Meredith Yeager, Youjin Wang, Stephen R. Spellman, Stephen J Chanock, Stephanie J. Lee, Sharon A Savage
Journal: Blood (2017)
HGG-29. VENETOCLAX SYNERGIZES WITH RADIATION THERAPY FOR THE TREATMENT OF DIPG
Authors: Ilango Balakrishnan, Senthilnath Lakshmana Chetty, Krishna Madhavan, Susan Fosmire, Angela Pierce, Faye walker, Nathan Dahl, Siddhartha Mitra, Rajeev Vibhakar, Sujatha Venkataraman
Journal: Neuro-Oncology (2021)

Abstract Background and Rationale Diffuse intrinsic pontine glioma (DIPG) is one of the most aggressive pediatric brain tumors. Currently, the main treatment for DIPG is radiation and it’s only a palliative care, as the tumor eventually becomes resistant to radiation. In this study we found that radiation leads to an increase in anti-apoptotic BH3 proteins mainly BCL2 in DIPG. Previous studies in other tumor types have shown that increase in these pro-survival BCL2 family members are associated with treatment resistance and poor prognosis. Therefore, we hypothesize that inhibition of BCL2 using a small-molecule inhibitor, venetoclax that crosses the blood-brain barrier, will represent a possible therapeutic strategy to overcome radiation resistance in DIPG. Approach: For in vitro studies, DIPG cells were exposed to different radiation doses (0–10 Gy) and the magnitude of the sensitizing effect of venetoclax (with IC15) was calculated by clonogenic assay. Evaluated BCL2 family proteins by western and cytotoxicity by cleaved caspase incucyte assays. For in vivo studies, NSG mice orthotopically engrafted with a human H3K27M-DIPG luciferase-expressing cells in the pons were exposed to a focal fractionated radiation of 2Gy/day for 3 days. Mice were randomized into 2 groups based on bioluminescence IVIS signal intensity; each group receiving either venetoclax (15 mg/kg, by i.p) 3 days/week for 10 weeks or vehicle. Decrease in tumor burden was measured by IVIS and survival was evaluated compared to vehicle treated mice. Results Single agent venetoclax showed no significant activity against DIPG tumors in in vitro and in vivo DIPG xenografts. Single-agent radiation cleared the tumor burden but only transiently. Combination of radiation with venetoclax showed considerable synergistic anti-tumor effect in vitro and in vivo leading to a significant increase in animal survival beyond either single agent treatments. The metabolic reprogramming that results in this enhanced cell-killing effect will be discussed.
Efficacy, treatment modalities, and safety of regorafenib in Chinese metastatic colorectal cancer patients: A multiple centers real-world study.
Authors: Zhichao Jiang, Yongkun Sun, Wen Zhang, Ning Liu, Wensheng Qiu, Tao Jiang, Sheng Li, Ning Sun, Xiaoyou Li, Liangjun Zhu, Zimin Liu, Ai-Ping Zhou
Journal: Journal of Clinical Oncology (2021)

e15569 Background: For patients with refractory metastatic colorectal cancer (mCRC) treatment with regorafenib improved the overall survival (OS) in two phase 3 trials. Regorafenib has been recognized as a standard third line treatment in mCRC. However, the efficacy and safety of regorafenib in real world for Chinese patients is lacking. Methods: Patients of mCRC treated with at least one cycle of regorafenib (40, 80, 120 or 160mg OD for 21 days, as a 28-day cycle) from August 2017 to June 2020 in three Chinese medical centers were enrolled. Data of demographic, treatment, dosimetry, safety and survival was collected retrospectively. The primary endpoint was OS. Secondary endpoints were progression free survival (PFS), objective response rate (ORR), disease control rate (DCR) and the incidence of adverse events (AEs). Results: 372 patients were enrolled, of whom 266 (71.5%) accepted regorafenib alone and 106 (28.5%) received combination therapy with regorafenib. In these patients, 75 (20.16%) and 275 (73.9%) patients received regorafenib as third or higher line treatment. Starting dose was 160mg in 93 (25.0%) patients, 120mg in 74 (19.9%) patients, 80mg in 142 (38.2%) patients and 40mg in 7 (1.9%) patients. The maintenance dose was confirmed in 236 patients. Among them, 111 (46.6%) and 75 (31.8%) accepted 80 and 120mg as the last daily dose. Only 50 (21.2%) patients could receive 160mg as a long-term therapy. Median follow-up time was 15.2 months. ORR and DCR were 3.8% and 55.3%. The mPFS was 3.1 months (95%CI: 2.50-3.53) and mOS was 10.2 months (95% CI: 9.27-11.93) . The mOS of 80, 120 and 160mg last daily dose were 10.5, 14.1 and 14.3 months, respectively. Patients received regorafenib in combination with other drugs including chemotherapy or PD-1 inhibitor had longer survival compared with regorafenib alone with mOS of 15.5 (95% CI: 10.1-19.0) and 9.7 months (95% CI: 7.8-11.0) (p = 0.004). The mOS of patients developed lung metastasis and the counterpart with liver metastasis was13.3 versus 9.7 months. The common AEs were anemia (26.1%), hyperbilirubinemia (25.3%), liver injury (24.7%), thrombocytopenia (18.0%) and recorded hand-foot skin reaction (HFSR) (19.6%). The most common grade 3-4 AEs included hyperbilirubinemia (3.5%), recorded HFSR (3.5%), anemia (2.2%) and thrombocytopenia (1.1%). Due to most patients was reviewed in clinic, some data of AEs was missing or incomplete. Conclusions: In the real world, regorafenib showed promising efficacy and manageable toxicities in Chinese patients with refractory mCRC. The dose of 120mg of regorafenib seemed to have a similar survival benefit compared with 160mg. In addition to a better tolerance, 120mg may be a more suitable dose for Chinese mCRC patients. Clinical trial information: NCT04735991. [Key words] Colorectal cancer; Regorafenib; Real world