tbuckley/cabot-search huggingface dataset:
Camrelizumab combined with SOX regimen in the first-line treatment of unresectable advanced or recurrent gastric cancer: A single-arm, prospective, open clinical study.
Authors: Zhengxiang Han
Journal: Journal of Clinical Oncology (2021)

e16017 Camrelizumab combined with SOX regimen in the first-line treatment of unresectable advanced or recurrent gastric cancer£ºA single-arm, prospective, open clinical study. Background: Gastric cancer is one of the most common malignant tumors of the digestive system. In China, 80% of patients with gastric cancer are already in advanced or locally advanced stage at the time of detection. Even after receiving radical gastrectomy, more than half of patients will have local recurrence or distant metastasis, and the 5-year survival rate of patients with gastric cancer with metastasis is less than 10%.In recent years, more and more evidence supports the application of immune checkpoint inhibitors in advanced gastric cancer.In 2020, PD-1 was approved for advanced gastric cancer receiving second-line or above treatment in China, which is an affirming of the efficacy of PD-1 in the clinical treatment of gastric cancer. Immunotherapy combined with conventional chemotherapy, this study aims to explore the efficacy and safety of PD1 combined with chemotherapy in the treatment of first-line gastric cancer. Methods: This was a single center, prospective clinical study conducted at the Affiliated Hospital of Xuzhou Medical University, Jiangsu Province.Patients with newly treated unresectable advanced or recurrent gastric or gastroesophageal junction adenocarcinoma were enrolled.All enrolled subjects were treated with camrelizumab combined with SOX regimen every 3 weeks.The primary endpoint was progression-free survival (PFS).Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.This study was registered at Chictr.org.cn with the number Chictr2000029691. Results: The study plans to enroll 30 patients, and 16 patients have been included in the study from March 2020 to December 2020. Among them, 7 patients can be evaluated, 14 males, 2 females, ECOG score 0 or 1. Of the 7 patients who can be evaluated for efficacy, 1 achieved PR and 5 achieved SD, ORR was 14.29%, and DCR was 85.71 %. This is the early stage of data analysis, PFS has not yet reached, and the side effects are mild, mainly with grade 1 adverse reactions. The most common AEs are neutropenia (3/7) and decreased appetite (2/7). There were no treatment-related deaths. Conclusions: This study provides preliminary evidence for the first-line treatment of unresectable advanced or recurrent gastric or gastroesophageal junction adenocarcinoma with camrelizumab combined with chemotherapy. The current number of enrolled cases is small, but the preliminary effect of immunotherapy combined with chemotherapy in first-line patients with advanced gastric cancer can still be seen. This trial will further explore the clinical efficacy and safety of immunotherapy in the first-line gastric cancer. Clinical trial information: ChiCTR2000029691.
Analysis of Survival Among Adults With Early-Onset Colorectal Cancer
Authors: Kirbi L. Yelorda, Sue J. Fu, Douglas K. Owens
Journal: JAMA Network Open (2021)

En Cheng, MD, PhD; Holly N. Blackburn, MD; Kimmie Ng, MD, MPH; Donna Spiegelman, ScD; Melinda L. Irwin, PhD, MPH; Xiaomei Ma, PhD; Cary P. Gross, MD; Fred K. Tabung, PhD, MSPH; Edward L. Giovannucci, MD, DrPH; Pamela L. Kunz, MD; Xavier Llor, MD, PhD; Kevin Billingsley, MD, MBA; Jeffrey A. Meyerhardt, MD, MPH; Nita Ahuja, MD, MBA; Charles S. Fuchs, MD, MPH
Radiomic features in recurrent/metastatic platinum refractory head and neck squamous cell carcinoma treated with immunotherapy.
Authors: Giuseppe Anile, Andrea Bettinelli, Marta Paiusco, Giorgio De Conti, Chiara Gottardi, Pierfranco Conte, Maria Grazia Ghi
Journal: Journal of Clinical Oncology (2021)

e18000 Background: Radiomics is the computerized extraction of quantitative features from medical images, beyond the level of detail accessible to an unaided human eye. Several studies on radiomic analysis have been carried out to identify predictive, prognostic and diagnostic biomarkers for diverse tumor types including HNSCC. Radiomic features proved to be effective in predicting outcomes in patients with locally advanced HNSCC. The aim of the present study was to dentify predictive and prognostic radiomic features in platinum-refractory HNSCC patients with recurrent and/or metastatic (R/M) disease treated with anti PD-1 monotherapy. Methods: We retrospectively reviewed the data of 38 patients treated with Nivolumab at our Institution between January 2018 and March 2020. Nasopharyngeal carcinomas were not eligible. CT radiomic textural features were extracted from regions of interests (ROIs) manually delineated around tumor volumes. Minimum Redundancy Maximum Relevance (mRMR) algorithm was the method of choice to rank radiomic features based on three outcomes: overall response rate (ORR); disease progression (PD) and overall survival (OS). Logistic regression was employed to build predictive/prognostic models. Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) was chosen as the metric to assess model performances. Results: Data from 29 out of 38 patients were ultimately analyzed. Nine patients were excluded due to nasopharynx as primary tumor site and/or inadequate CT scan imaging. A total of 57 ROIs were extracted and analyzed. We obtained 9 models: 3 radiomic models, 3 clinical models and 3 combined models (radiomic plus clinical) for each outcome of interest (ORR, PD, OS). In the radiomic models 2 features were identified as predictor for ORR (AUC 0.69), 1 radiomic feature was predictive for PD (AUC 0.83) and 1 predictive for OS (AUC 0.72). In the clinical models, 3 clinical characteristics were identified for both ORR (AUC 0.91) and PD (AUC 0.73) and 2 clinical features were found to be predictive for OS (AUC 0.91). The combined model identified 3 features (2 radiomics and 1 clinical) predictive for ORR (AUC 0.76). No clinical characteristics were found in the combined model for PD. No radiomics features have been shown to be related to OS. Conclusions: This is an explorative study to test the power of radiomics and the potential value of combining radiomics and clinical data as a prognostic and predictive instrument. In this small sample size, the quantitative analysis of CT images seems to be an interesting tool which has to be further explored as predictor of outcome in a larger series of patients.[Table: see text]
In vivo urinary compatibility of Mg-Sr-Ag alloy in swine model
Authors: Di Tie, Norbert Hort, Minfang Chen, Renguo Guan, Sviatlana Ulasevich, Ekaterina V. Skorb, Dapeng Zhao, Yili Liu, Patricia Holt-Torres, Huinan Liu
Journal: Bioactive Materials (2021)

A biodegradable metallic ureteral stent with suitable mechanical properties and antibacterial activity remains a challenge. Here we reveal the scientific significance of a biodegradable Mg-Sr-Ag alloy with a favorable combination of balanced mechanical properties, adjustable indwelling time in urinary tract and evident antibacterial activity via in vivo experiments in a swine model. Attributed to the rheo-solidification process, equiaxial microstructure and significantly refined grains (average grain size: 27.1 μm) were achieved. Mg17Sr2 and Mg4Ag were found as the primary precipitates in the matrix, due to which the alloy obtained ca. 111% increase in ultimate tensile strength in comparison to pure magnesium. Both the in vitro and in vivo results demonstrated the satisfactory biocompatibility of the alloy. Histological evaluation and bioindicators analysis suggested that there was no tissue damage, inflammation and lesions in the urinary system caused by the degradation process. The stent also improved the post-operative bladder functions viewed from the urodynamic results. Our findings highlight the potential of this alloy as antibacterial biodegradable urinary implant material.
Detection of surface molecules and phosphorylation events by surface enhanced raman scattering (SERS) using composite organic-inorganic nanoparticles (COINs) in single cells.
Authors: Catherine Shachaf, Sailaja Elchuri, Jing Zhu, Lienchi Nguyen, Jingwu Zhang, Lei Sun, Salena Chang, Garry Nolan
Journal: Cancer Research (2008)

4742  To better understand the processes occurring in abnormal cells compared to normal cells, there is an urgent need to improve the technology for simultaneous detection of multiple events in a single cell. To better characterize several different events that occur in a single cell at a given time, we need to be able to accurately detect and analyze several nodes concurrently. Currently, immuno-detecton assays are used with fluorescence tags. Fluorescent molecules have broad and overlapping spectra.  We have developed “Composite Organic-Inorganic Nanoparticles” (COINs) Raman nanoparticles for immuno-detection assays of extra- and intra-cellular proteins in single cells. COINs are Surface-Enhanced Raman Scattering (SERS) silver particle clusters with incorporated Raman labels. Each COIN has a unique Raman spectral fingerprint, which allows higher levels of multiplexing. To measure Raman spectra in single cells we have built an Integrated Raman BioAnalyzer (IRBA). The IRBA is a low noise, high sensitivity, automated and compact Raman Spectrometer for biomedical applications.  We tested the ability of antibody-conjugated COINs to detect surface antigens by recognizing the CD54 antigen that is expressed on U937 monocytic leukemia cells compared to the CD8 antigen that is not expressed on U937 cells in single cell immunoassays. We determined the cell specific detection of the CD54 antigen on U937 expressing cells compared to non-expressing H82 small cell lung cancer cells.  To evaluate the COIN Raman technology for detecting specific populations in primary human cells we identified CD8 expressing T-cells among a heterogeneous population of primary human peripheral blood mononuclear cells (PBMC). Finally, we used COINs to measure intracellular phosphorylation in cells. We treated U937 cells with IFNγ and IL-4 cytokines and measured changes in Stat1 (Y701) and Stat6 (Y641) phosphorylation. We found a six-fold increase in Stat1 phosphorylation and a three-fold increase in Stat6 phosphorylation with COINs; both are comparable to the fluorescence signals measured by flow cytometry. We confirmed the utility of COINs in a multiplex assay by simultaneous detection of pStat1 (BFU) and pStat6 (AOH) in single cells.  We have demonstrated the feasibility and practicality of using COINs for cell surface marker analysis and for measuring changes in intracellular phosphorylation. The COIN Raman nanoparticles offer new possibilities to expand on the current fluorescent technology used for immunoassays in single cells.
Gefitinib With Concurrent Thoracic Radiotherapy in Unresectable Locally Advanced NSCLC With EGFR Mutation; West Japan Oncology Group 6911L
Authors: Hiroaki Akamatsu, Haruyasu Murakami, Hideyuki Harada, Junichi Shimizu, Hidetoshi Hayashi, Haruko Daga, Yoshikazu Hasegawa, Young Hak Kim, Terufumi Kato, Shoji Tokunaga, Yasumasa Nishimura, Nobuyuki Yamamoto, Kazuhiko Nakagawa
Journal: Journal of Thoracic Oncology (2021)

IntroductionAbout 10% of patients with locally advanced NSCLC (LA-NSCLC) harbor EGFR mutation and recent reports suggested the declined benefit with an immune checkpoint inhibitor in this population. The attempt that introduces EGFR tyrosine kinase inhibitor into the treatment of LA-NSCLC with EGFR mutation has been warranted.MethodsChemotherapy-naive patients with unresectable LA-NSCLC with sensitive EGFR mutation (exon 19 deletion or exon 21 L858R point mutation) were enrolled. Patients were treated with gefitinib (250 mg/d for 2 y) plus concurrent thoracic radiotherapy (64 Gy/32 fractions). The primary end point was progression-free survival (PFS) at 2 years (trial identifier, UMIN000008366).ResultsBetween August 2012 and November 2017, a total of 28 patients were enrolled and 27 were eligible. The median age was 67 years (range: 45–74); never/current or former smoker in 15/12 patients, respectively; Eastern Cooperative Oncology Group performance status of 0/1 in 19/8; EGFR exon 19 deletion/exon 21 L858R in 13/14; and c-stage IIIA/IIIB in 14/13. The PFS rate at 2 years by independent review was 29.6% (one-sided 95% confidence interval [CI]: 17.6%–). The overall response rate was 81.5% (95% CI: 63.3%–91.3%), median PFS was 18.6 months (95% CI: 12.0–24.5 mo), and median overall survival was 61.1 months (95% CI: 38.1 mo–not reached). Approximately half of the patients exhibited solitary brain metastasis as their first site of relapse. Adverse events greater than or equal to grade 3 were fatigue, skin reaction, and appetite loss (3.7% each).ConclusionsThis prospective study revealed the tolerability and the possible efficacy of gefitinib plus concurrent thoracic radiotherapy in patients with LA-NSCLC having EGFR mutation.
Safety and efficacy of chidamide in combination with decitabine plus anti-PD-1 camrelizumab after relapse or progression on decitabine-plus-camrelizumab in classical Hodgkin lymphoma.
Authors: Chunmeng Wang, Jing Nie, Yang Liu, Qingming Yang, Weidong Han
Journal: Journal of Clinical Oncology (2021)

e19515 Background: The anti-PD-1 combination therapy significantly improves clinical outcomes in patients with relapsed/refractory classical Hodgkin lymphoma (cHL), and up to 71% of patients who receive decitabine-plus-anti-PD-1 camrelizumab could achieve a complete response. However, a subset of patients is recalcitrant to decitabine-plus-camrelizumab and half of patients might experience disease progression within three years. Effective treatment regimens for those with relapsed or progressive cHL who failed decitabine-plus-camrelizumab are needed. This Phase II study was designed to assess the safety and efficacy of the combination of decitabine-plus-camrelizumab and chidamide, a histone deacetylase inhibitor, in decitabine-plus-camrelizumab resistant cHL patients. Methods: Patients with relapsed/refractory cHL who had primary resistance or progressed/relapsed on decitabine-plus-camrelizumab were enrolled and administrated with chidamide at 10 mg (days 1 to 4) and 20 mg (days 8, 11,15 and 18); plus decitabine at 10 mg (days 1 to 5); and camrelizumab at 200 mg (day 6), every 3 weeks. Safety was assessed by CTCAEv5.0, and antitumor response by PET-CT according to the revised Lugano classification. The primary endpoint was objective response rate. Recruitment is ongoing. This trial is registered with ClinicalTrial.gov number, NCT04233294. Results: Between January 19, 2020, and January 31, 2021, nineteen patients with relapsed/refractory cHL after relapse or progression on decitabine-plus-camrelizumab were enrolled. A median of 20 cycles of prior decitabine-plus-camrelizumab was given (range, 4-28). Fourteen patients completed response evaluation with a median follow-up of 5.7 months. All eligible patients received this triplet-agent regimen with a median of 8 cycles (range, 3 to 12). Thirteen of the fourteen evaluated patients (93%) had an objective response, including six acquiring a complete remission (43%) and seven reaching a partial response (50%). The most common adverse events were leukocytopenia (58%; grade 3: 16%), nausea (53%) and hypertriglyceridemia (26%). No immune-related adverse events were observed. Conclusions: The preliminary result shows a high objective response rate with the combination of chidamide, decitabine and camrelizumab in patients with resistance to decitabine-plus-camrelizumab therapy. The addition of chidamide to decitabine-plus-camrelizumab has an acceptable safety profile, and does not trigger immune-related adverse events. Clinical trial information: NCT04233294.
Prognostic role of apolipoprotein and lactate dehydrogenase levels in resectable colorectal cancer.
Authors: Yifei Ma, Ping Lu, Xinjun Liang, Shaozhong Wei
Journal: Journal of Clinical Oncology (2021)

e15541 Background: Apolipoprotein b (apob), apolipoprotein a1 (apoa1), and lactate dehydrogenase (LDH) levels are circulating biomarkers that relate to tumor inflammation. This study aimed to evaluate the prognostic role of apob/apoa1 and LDH in resectable colorectal cancer (CRC). Methods: 513 patients of colorectal cancer (CRC) from Hubei cancer hospital were included finally, and we collected the pre-operative laboratory results within a week before surgery. We combined the two indicators and divided them into three groups (group 1: apob/apoa1-LDH low; group 2: apob/apoa1 or LDH high; group 3: apob/apoa1-LDH high). Kaplan-Meier survival analysis, univariate COX regression and multivariate COX regression were used to assess the prognoses of colorectal cancer patients. Results: The median follow-up was 35 months. Our study found that the prognosis of group 1 was better than group 2 in both overall survival (88.2% vs. 75.4% vs. 61.9%) (P≤0.001) and diseases-free survival (77.4% vs. 64.7% vs. 42.8%) (P≤0.001), and group 3 was the worst. By multivariate analysis, the new predictive marker obtained by combining apob/apoa1 and LDH could independently predict outcomes in CRC [overall survival: (HR: 1.487; 95% CI, 1.074-2.061); diseases-free survival (HR: 1.381; 95% CI, 1.045-1.827)]. Conclusions: New marker based on apob/apoa1 and LDH is useful for predicting the prognosis of patients with CRC. However, more research is needed in the future.
Intranasal infusion of GD3 and GM1 gangliosides downregulates alpha-synuclein and controls tyrosine hydroxylase gene in a PD model mouse
Authors: Yutaka Itokazu, Takahiro Fuchigami, John C. Morgan, Robert K. Yu
Journal: Molecular Therapy (2021)

Parkinson's disease (PD) is characterized by Lewy bodies (composed predominantly of alpha-synuclein [aSyn]) and loss of pigmented midbrain dopaminergic neurons comprising the nigrostriatal pathway. Most PD patients show significant deficiency of gangliosides, including GM1, in the brain, and GM1 ganglioside appears to keep dopaminergic neurons functioning properly. Thus, supplementation of GM1 could potentially provide some rescuing effects. In this study, we demonstrate that intranasal infusion of GD3 and GM1 gangliosides reduces intracellular aSyn levels. GM1 also significantly enhances expression of tyrosine hydroxylase (TH) in the substantia nigra pars compacta of the A53T aSyn overexpressing mouse, following restored nuclear expression of nuclear receptor related 1 (Nurr1, also known as NR4A2), an essential transcription factor for differentiation, maturation, and maintenance of midbrain dopaminergic neurons. GM1 induces epigenetic activation of the TH gene, including augmentation of acetylated histones and recruitment of Nurr1 to the TH promoter region. Our data indicate that intranasal administration of gangliosides could reduce neurotoxic proteins and restore functional neurons via modulating chromatin status by nuclear gangliosides. Parkinson's disease (PD) is characterized by Lewy bodies (composed predominantly of alpha-synuclein [aSyn]) and loss of pigmented midbrain dopaminergic neurons comprising the nigrostriatal pathway. Most PD patients show significant deficiency of gangliosides, including GM1, in the brain, and GM1 ganglioside appears to keep dopaminergic neurons functioning properly. Thus, supplementation of GM1 could potentially provide some rescuing effects. In this study, we demonstrate that intranasal infusion of GD3 and GM1 gangliosides reduces intracellular aSyn levels. GM1 also significantly enhances expression of tyrosine hydroxylase (TH) in the substantia nigra pars compacta of the A53T aSyn overexpressing mouse, following restored nuclear expression of nuclear receptor related 1 (Nurr1, also known as NR4A2), an essential transcription factor for differentiation, maturation, and maintenance of midbrain dopaminergic neurons. GM1 induces epigenetic activation of the TH gene, including augmentation of acetylated histones and recruitment of Nurr1 to the TH promoter region. Our data indicate that intranasal administration of gangliosides could reduce neurotoxic proteins and restore functional neurons via modulating chromatin status by nuclear gangliosides.
Abstract 14614: Transcatheter Aortic Valve Replacement Reduces Inpatient Costs and Length of Stay for Cancer Patients With Severe Aortic Stenosis
Authors: Logan Hostetter, Dominique Monlezun, Tariq Thannoun, Krishna Pabba, Sean M Lawless, Ritesh Patel, Cullen Grable, Danyi Zheng, Natalie Chen, Nicolas Palaskas, Juan Lopez-Mattei, Peter Kim, Mehmet Cilingiroglu, Konstantinos Marmagkiolis, Cezar Iliescu
Journal: Circulation (2019)

Introduction: Transcatheter aortic valve replacement (TAVR) has been shown to be clinically and financially superior to surgical AVR (SAVR) in severe aortic stenosis (SAS), even in patients at low ...
Irradiated esophageal squamous cell carcinoma cells induced the increase of Treg by TGF-beta.
Authors: Yuan Wang, Tao Li, Jiahua Lv, Ling Xiao
Journal: Journal of Clinical Oncology (2021)

e16092 Background: The infiltration of CD4+CD25+Foxp3+ regulatory T cells (Treg) in the tumor microenvironment is one of the main reasons for radiation resistance and tumor recurrence after radiotherapy. It has been established that Treg is more resistant to radiation than other T cells, but the proliferation of immune cells after radiotherapy is affected by other factors, including tumor cells. Treg frequency in the tumor microenvironment after radiotherapy has not been defined. We studied the effect and mechanism of esophageal squamous cell carcinoma on Treg cells after radiation. Methods: After 2Gy irradiation, TE-1 cells were co-cultured with normal peripheral blood lymphocytes for 48 hours. Flow cytometry was used to detect Treg/CD4+T cell frequency. The mRNA expression of TGF-β1/2 in TE-1 was detected by qPCR, and the protein content of TGF-β1/2 in the medium was detected by ELISA. Results: Compared with non-irradiation group, the expression of TGF-β1 and TGF-β2 in TE-1 cells of irradiation group increased, and the protein content of TGF-β1 and TGF-β2 in culture medium increased, the difference was statistically significant(P &lt; 0.001). Flow cytometry showed that CD4+CD25+/CD4+Tcell and CD4+CD25+Foxp3+/CD4+Tcell were increased in the radiotherapy group after co-culture, and the difference was statistically significant(P &lt; 0.001). Conclusions: The expression of TGF-β1 and TGF-β1 in esophageal squamous cell carcinoma cells increased after irradiation, and the frequency of Treg induced by co-culture increased, suggesting that esophageal squamous cell carcinoma cells after radiotherapy can induce the increase of Treg cells, which may be achieved mainly through the mechanism of increasing the secretion of TGF-β1/2.
Characteristics of Males with Hemophilia in the United States Hemophilia Treatment Center Network (USHTCN) with New-Onset Elevated Inhibitor Titers, December 15, 2013 - December 31, 2016
Authors: Marilyn J Manco-Johnson, J. Michael Soucie, Anjali Sharathkumar, Fiona Bethea, Christine L Kempton, Amanda B. Payne, Michael Wang, Connie H Miller
Journal: Blood (2017)