tbuckley/cabot-search huggingface dataset:
83P Correlation of C-Myc with Epithelial-Mesenchymal Transition Phenotype
Authors: A.M. Supernat, A. Markiewicz, A. Sejda, B. Seroczynska, J. Skokowski, J. Szade, M. Welnicka-Jaskiewicz, P. Nastaly, N. Bednarz-Knoll, A.J. Zaczek
Journal: Annals of Oncology (2012)
Charles Arthur Veys
Authors: Peter Croft, Jane Veys, Paul Veys
Journal: BMJ (2020)

Charles Arthur Veys (“Carl”) was born in Antwerp, the middle of three French speaking brothers, to Belgian parents (Marcel and Madeleine), who had managed to bridge the French/Flemish divide. In 1935 the family moved to Sheffield, where Marcel, an engineer who had qualified from Louvain University, joined Tinsley Wire Industries as chief executive. As a young boy in the later war years, Charles accompanied his father on weekend factory visits, and concern about the impact of working conditions on employees’ health was to inspire and shape the direction and drive of Charles’s future medical career.

Charles and his brothers were educated at a Jesuit boarding school, Mount St Mary’s, on the outskirts of Sheffield, safe from the bombing of the city. Charles went on to study medicine at Liverpool University. There he met Sally Sutton, the nurse who accepted his offer of help in cleaning the operating theatre and his subsequent proposal of marriage, a happy union that was to last until his death more than 60 years later.

Charles’ first job was national service and he chose a three year medical posting to Tanganyika, now Tanzania, so that Sally could go with him. His main responsibility was the health of 700 King’s African Rifles troops and their families, but he did find time to prescribe Dover’s powder for an ailing John Wayne on the film set of Hatari . He also set out to earn the trust of the local Masai community by learning Swahili, while his wider interest …
Lessons Learned from the Australian Bushfires
Authors: Sotiris Vardoulakis, Guy Marks, Michael J. Abramson
Journal: JAMA Internal Medicine (2020)

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Prospective comparison of 68Ga-RM2 PET/CT and 68Ga-PSMA-617 PET/CT for initial staging of prostate cancer.
Authors: Romain Schollhammer, Henri De Clermont-Gallerande, Gregoire Robert, Mokrane Yacoub, Frederic Lamare, Nicolas Balamoutoff, Delphine Vimont, Elif Hindie, Philippe Fernandez, Clément Morgat
Journal: Journal of Clinical Oncology (2020)

21 Background: PSMA ( Prostate Specific Membrane Antigen) and GRP-R ( Gastrin Releasing Peptide Receptor) are overexpressed on prostatic cancer cells and can be targeted with a PSMA inhibitor such as 68 Ga-PSMA-617 (Liu 2018) or a GRP-R antagonist such as 68 Ga-RM2 (Touijer 2019). We aimed to compare 68 Ga-PSMA-617 PET/CT and 68 Ga-RM2 PET/CT at initial staging of prostate cancer. Methods: We prospectively enrolled 10 treatment-naïve patients with biopsy-confirmed prostate cancer. Fifteen lesions were found (two with Gleason score (GS) 6; seven GS 7(3+4), two GS 7(4+3) and four GS ≥ 8). 68 Ga-PSMA-617 PET/CT and 68 Ga-RM2 PET/CT were randomly performed before prostatectomy with imaging at 1 and 2 hours after injection (2MBq/kg). Manual (MS) and automatic (AS) segmentation were performed on each PET imaging and then compared to histology (standard-of- truth). Prostatectomy samples were analyzed by an experimented pathologist who identified and staged each lesion according to GS. Each prostatectomy slice available was scanned for comparison between PET and histologic segmentation. Uptake intensity (SUVmax) and signal-to-noise ratio (SNR) relative to non-lesional prostate gland parenchyma were analyzed. Per-lesion analysis was performed on final GS (prostatectomy). Results: Using AS, 68 Ga-RM2 PET/CT showed better sensitivity (Se) than 68 Ga-PSMA-617 PET/CT: (0.85 vs 0.75) and better specificity (Sp) (0.89 vs 0.60). MS found similar Se (0.94 vs 0.93) but better Sp (0.89 vs 0.80) with 68 Ga-RM2 PET/CT. SNR of 68 Ga-RM2 PET/CT was high whatever the GS was; while 68 Ga-PSMA-617 PET/CT exhibited higher SNR in high GS (p = 0.044). Finally, in low GS, SNR of 68 Ga-RM2 PET/CT was significantly higher than 68 Ga-PSMA-617 PET/CT (p = 0.004). Conclusions: GRP-R-targeting and PSMA-targeting have been previously compared in patients with biochemically recurrence (Minamimoto 2016) but not at primary staging. Our initial results, in this indication, showed great diagnostic performance of 68 Ga-RM2 PET/CT compared to 68 Ga-PSMA-617 PET/CT to characterize low Gleason score tumors. 68 Ga-PSMA-617 PET/CT is promising for initial staging of high Gleason score tumors. These results need to be confirmed in a larger study.
Circulating ensembles of tumor-associated cells in genitourinary cancers.
Authors: Ajay Srinivasan, Dadasaheb B. Akolkar, Pradip Fulmali, Pooja Fulmali, Navin Srivastava, Darshana Patil, Revati Patil, Sachin Apurwa, Sanket Patil, Shoeb Patel, Vineet Datta, Cynthe Sims, Rajan Datar
Journal: Journal of Clinical Oncology (2020)

718 Background: Detection of genitourinary cancers is based on histopathological analysis of tumor tissue obtained by invasive biopsies following manifestation of clinical or radiological symptoms. There is presently no non-invasive blood-based test with high specificity and sensitivity for detection of genitourinary cancers. Considering that unprovoked thromboembolism is a significant risk in multiple cancers, we hypothesized that tumor derived circulating emboli in peripheral blood could comprise cancer cells and would serve as a reliable biomarker for detection of genitourinary cancers. These Circulating Ensembles of Tumor Associated Cells (C-ETACs) are defined as clusters of 3 or more cells of tumorigenic origin (EpCAM+, CK+ and CD45±). Methods: We obtained 15ml of blood from 8828 individuals, including 103 cases of Renal cancer, 79 cases of bladder cancer, 153 cases of prostate cancers as well as from 8493 asymptomatic individuals with age related elevated risk and were negative in various screening investigations (CEA, AFP, CA19-9, CA125, PSA, LDCT, Mammography, PAP Smear). PBMC were isolated by centrifugation. C-ETACs were enriched, harvested and characterized by immunofluorescence staining for EpCAM, CK, CD45 as well as organ specific markers for renal, bladder and prostate cancers. Results: C-ETACs were detected in 87 (84.5%) of 103 renal cancers, 71 (89.9%) of 79 bladder cancers and 138 (90.2%) of 153 prostate cancers respectively irrespective of extent (stage / metastatic status) of disease and prior treatments. Overall sensitivity among 335 cancer patients was 88.4%. Among the 8493 asymptomatic individuals, C-ETACs were detected in 255 individuals (97% specificity). Conclusions: C-ETACs were ubiquitously detected in cancers of Kidney, Bladder and Prostate regardless of stage and treatment status, and pose significant latent risk of metastasis/recurrence. The relative undetectability of C-ETACs in the asymptomatic cohort indicates causative connection with malignancies and are hence suitable for screening for these cancers.
Quality of life outcomes from a phase III trial exploring optimal sequencing of androgen deprivation therapy with external beam radiotherapy in localized prostate cancer.
Authors: Soumyajit Roy, Scott Grimes, Libni Eapen, Choan E, Kyle Malone, Julia Craig, Scott Carlyle Morgan, Shawn Malone
Journal: Journal of Clinical Oncology (2020)

315 Background: Dose-escalated prostate radiotherapy (PRT) with androgen deprivation therapy (ADT) is a standard curative treatment for localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. We report the patient-reported health related quality of life (HR-QoL) outcomes from a phase III study exploring optimal sequencing of PRT with ADT in LPCa. Methods: Newly diagnosed LPCa patients with Gleason score ≤7, clinical stage T1b-T3a, and PSA &lt; 30 ng/mL were randomized to receive PRT (76 Gy/38 fractions) with 6 months (mos) of ADT starting 4 mos prior to RT (NAHT arm) or concurrently with RT (CAHT arm). HR-QoL was assessed using EORTC QLQ-C30 and PR25 at baseline, q2 mos while on ADT, q4 mos for year 1 and 2 after ADT, q6 mos from year 3 to 5 and annually thereafter. Linear mixed modelling was applied to compare change in score (relative to baseline) over time. Wilcoxon rank-sum test was used to identify between-group difference in absolute scores, at 18, 36 and 60 mos. The statistical and clinical significance was set at p≤0.01 and 10-point threshold, respectively. Results: Overall 432 men were enrolled in the study and 393 (194 in NAHT and 199 in CAHT arm) were eligible for HR-QoL evaluation. There was a significant difference in the change in score of sleep disturbance due to urinary bother (least-squared mean: 3.9 vs. 7.6, P = 0.001) between the two arms. Although there were statistically significant differences in absolute scores of global QoL (18, 60 mos), cognitive (18, 60 mos), social and emotional functions (60 mo), sexual intimacy (18 mo) and fatigue (60 mo) favoring NAHT, the only clinically meaningful difference was noted in ejaculatory dysfunction at 18 (mean: 52.5 vs. 64.6), 36 (60.2 vs. 49.2) &amp; 60 mos (61.4 vs. 50.9), respectively. Conclusions: We did not find any notable difference between the two arms with respect to score change over time in any of the HR-QoL metrics except sleep disturbance due to urinary bother. Clinically meaningful difference was noted only in the late absolute ejaculatory dysfunction score which favored the NAHT arm. Based on these findings, both NAHT and CAHT with PRT are reasonable standards of care for LPCa. Clinical trial information: DC-990-0082.
BIVV001, a new class of factor VIII replacement for hemophilia A that is independent of von Willebrand factor in primates and mice
Authors: Ekta Seth Chhabra, Tongyao Liu, John Kulman, Susannah Patarroyo-White, Buyue Yang, Qi Lu, Douglas Drager, Nancy Moore, Jiayun Liu, Amy M. Holthaus, Jurg M. Sommer, Ayman Ismail, Deana Rabinovich, Zhan Liu, Arjan van der Flier, Allison Goodman, Chris Furcht, Mark Tie, Tyler Carlage, Randy Mauldin, Terrence M. Dobrowsky, Zhiqian Liu, Oblaise Mercury, Lily Zhu, Baisong Mei, Volker Schellenberger, Haiyan Jiang, Glenn F. Pierce, Joe Salas, Robert Peters
Journal: Blood (2020)
Wnt-mediated endothelial transformation into mesenchymal stem cell–like cells induces chemoresistance in glioblastoma
Authors: Menggui Huang, Duo Zhang, Janet Y. Wu, Kun Xing, Eujin Yeo, Chunsheng Li, Lin Zhang, Eric Holland, Lutian Yao, Ling Qin, Zev A. Binder, Donald M. O’Rourke, Steven Brem, Constantinos Koumenis, Yanqing Gong, Yi Fan
Journal: Science Translational Medicine (2020)

Therapeutic resistance remains a persistent challenge for patients with malignant tumors. Here, we reveal that endothelial cells (ECs) acquire transformation into mesenchymal stem cell (MSC)-like cells in glioblastoma (GBM), driving tumor resistance to cytotoxic treatment. Transcriptome analysis by RNA sequencing (RNA-seq) revealed that ECs undergo mesenchymal transformation and stemness-like activation in GBM microenvironment. Furthermore, we identified a c-Met-mediated axis that induces β-catenin phosphorylation at Ser675 and Wnt signaling activation, inducing multidrug resistance-associated protein-1(MRP-1) expression and leading to EC stemness-like activation and chemoresistance. Last, genetic ablation of β-catenin in ECs overcome GBM tumor resistance to temozolomide (TMZ) chemotherapy in vivo. Combination of Wnt inhibition and TMZ chemotherapy eliminated tumor-associated ECs, inhibited GBM growth, and increased mouse survival. These findings identified a cell plasticity-based, microenvironment-dependent mechanism that controls tumor chemoresistance, and suggest that targeting Wnt/β-catenin-mediated EC transformation and stemness activation may overcome therapeutic resistance in GBM.
Successful treatment of refractory Barrett’s neoplasia with hybrid argon plasma coagulation: a case series
Authors: Arvind J. Trindade, Diana Wee, Praneet Wander, Molly Stewart, Calvin Lee, Petros C. Benias, Matthew J. McKinley
Journal: Endoscopy (2020)

A 60-year-old woman with Barrett's esophagus (Prague class C8M10) with flat high grade dysplasia underwent radiofrequency ablation (RFA) therapy. She underwent four sessions with the circumferential balloon and one treatment with the focal 90 ablation catheter for a total of five sessions. Sessions were performed every 3 months and the patient adhered to maximal acid suppression therapy.
How Reaction Severity Is Affected By Cofactors And Repeat Challenges: A Prospective Study Of Peanut Allergic Adults
Authors: Shelley Dua, James DOwey, Monica Ruiz Garcia, Simon Bond, Stephen Durham, Ian Kimber, Clare Mills, Graham Roberts, Isabel Skypala, James Wason, Pamela Ewan, Robert Boyle, Andrew Clark
Journal: Journal of Allergy and Clinical Immunology (2020)
Asthma-Related Outcomes in A Real-World Study of MP-AzeFlu to Treat Allergic Rhinitis
Authors: Ludger Klimek, Petr Cap, Gabriella Galffy, Melanie Emmeluth, Arkady Koltun, Ferdinand Kopietz, Duc Tung Nguyen, Hans Christian Kuhl, Ranny Van Weissenbruch, Wolfgang Pohl, David Price, Glennis Scadding, Joaquim Mullol
Journal: Journal of Allergy and Clinical Immunology (2020)
Simultaneous Home Care project for frail advanced cancer patients: a model of integration between no profit and Public Health System
Authors: C. Chini, L. Bascialla, S. Gobba, A. Tuzi, G. Tinelli, R. Pomarico, N. Giani, M. Flore, S. Reato, G. Pinotti
Journal: Annals of Oncology (2017)
Targeting tumor-associated macrophage (TAM) mediated inhibition of T-cell migration in prostate cancer using epigenetic modifying agents.
Authors: David Kosoff, Leigh Ellis, David J. Beebe, Joshua Michael Lang
Journal: Journal of Clinical Oncology (2020)

166 Background: Cytotoxic T lymphocytes (CTLs) perform vital anti-tumor functions and are critical to the efficacy of many anticancer therapies. In prostate cancer, the characteristic paucity of activated CTLs within the tumor microenvironment (TME) may be a key factor in disease progression and likely underlies the limited role for immune checkpoint inhibitors (ICIs) in prostate cancer treatment. In this study, we utilized novel microfluidic technologies to evaluate whether TAMs may be driving the exclusion of T cells from the prostate TME and whether the immunosuppressive functions of TAMs could be modified by epigenetic modifying agents. Methods: Primary macrophages and autologous T cells were derived from peripheral blood samples of prostate cancer patients at the University of Wisconsin. Mono-, co-, and tri-culture systems of macrophages, T cells, and 22RV1 cells (androgen-dependent prostate cancer cell line) were cultured in 2D and 3D in microfluidic cell culture platforms. Culture systems were treated with the EZH2 inhibitors (EZH2i) DZNep or EPZ-6438 or left untreated. Macrophages were also treated with M1 (IFN-g) and M2 (IL-4) polarizing cytokines. Systems were analyzed for T cell migration as well as mRNA and protein expression in each cell population. Results: Autologous macrophages inhibited activated T cell migration towards tumor cells in a multi-cellular microscale TME. T cell migration was restored through treatment with EZH2i. Gene expression analysis identified that EZH2i altered macrophage gene expression in the unpolarized and M1/M2 polarized states. In particular, there was increased expression of genes involved in T cell recruitment/chemotaxis, including CXCL10, CXCL11, CXCL12, following EZH2i treatment. Conclusions: We used novel microfluidic technologies to model and analyze multicellular TMEs using primary, patient-derived cells. We demonstrate that TAM-mediated suppression of T cell migration is mediated, in part, through epigenetic pathways, which can be targeted with EZH2i. Treatment with EZH2i, alone or in combination other therapies such as ICIs, may enhance cytotoxic T cell migration and activity in primary prostate cancer.
Des Spence: Why #healthbeliefs should be top of all our communications
Authors: Des Spence
Journal: BMJ (2020)

It was 1986—before the preferred pronoun, when # was an obscure wannabe on life’s keyboard, and when avocados were never crushed but were eaten unripe at Christmas, with prawns and Marie Rose sauce.

I reached for my near empty packet of Marlboro beside a mug full of cigarette ends. I struck a match, being careful not to torch my “big hair” laden with product, and twisted my earring anxiously, thinking how it didn’t suit me. I clasped my cigarette stained hands together and pressed them to my head, praying to God that the brachial plexus wouldn’t come up in …
Phase Ib/II Clinical Trial of Pembrolizumab With Bevacizumab for Metastatic Renal Cell Carcinoma: BTCRC-GU14-003
Authors: Arkadiusz Z. Dudek, Li C. Liu, Shilpa Gupta, Theodore F. Logan, Eric A. Singer, Monika Joshi, Yousef N. Zakharia, Joshua M. Lang, James K. Schwarz, Anas Al-Janadi, Ajjai S. Alva
Journal: Journal of Clinical Oncology (2020)

We hypothesized that bevacizumab will potentiate activity of pembrolizumab. We conducted a phase Ib/II, single-arm, multisite clinical trial of the combination in metastatic renal cell carcinoma (RCC).
Combination of AMG 160, a PSMA x CD3 half-life extended bispecific T-cell engager (HLE BiTE) immune therapy, with an anti-PD-1 antibody in prostate cancer (PCa).
Authors: Katherine L. Paweletz, Shyun Li, Julie M. Bailis, Gloria Juan
Journal: Journal of Clinical Oncology (2020)

155 Background: AMG 160 is an HLE BiTE immune therapy that binds prostate-specific membrane antigen (PSMA) on tumor cells and CD3 on T cells, leading to T cell activation, cytokine production, and tumor cell lysis. A phase 1 study of AMG 160 in patients with metastatic castration-resistant PCa is ongoing (NCT03792841). We investigated whether the combination of AMG 160 and an anti-PD-1 antibody could increase AMG 160 cytotoxicity against PCa cells in vitro and ex vivo. Methods: C4-2B human PCa cells engineered to overexpress PD-L1 were treated with a range of AMG 160 doses (0.144–30,000 pM) +/– a fixed dose of anti-PD-1 in the presence of activated human T cells. Cell viability was assessed by Steady-Glo after 1 day. PD-1 expression on T cells was evaluated by flow cytometry. A human tumor explant model consisting of thin sections of fresh surgically resected human PCa tumors was also used to evaluate the AMG 160 + anti-PD-1 combination. Explants were incubated in media over 2 days and treated with buffer alone, AMG 160, or AMG 160 + anti-PD-1 at fixed doses. Activation of autologous T cells within the tumor slices was assayed by flow cytometry, and secretion of cytokines into culture supernatants was measured by Meso Scale Discovery (MSD). Immune-response profiles of the culture tissues were assessed by NanoString. Results: In the PCa in vitro study, AMG 160 treatment induced upregulation of PD-1 on T cells. Cotreatment with AMG 160 + anti-PD-1 increased the potency of cell killing by 2–5x and killed a greater percentage of cells than AMG 160 alone. In the tumor explant model, which preserves tumor architecture and microenvironment, AMG 160 treatment induced activation of the autologous infiltrating T cells, and this activation was increased by cotreatment with anti-PD-1. AMG 160 treatment increased cytokine production, and cotreatment of tumor explants with AMG 160 + anti-PD-1 increased cytokine production further. Conclusions: Together these data suggest that antitumor efficacy of the AMG 160 HLE BiTE immune therapy can be increased by co-treatment with anti-PD-1. These data provide a rationale for evaluating this combination in future clinical studies.
Preoperative metastatic disease burden to predict overall survival following cytoreductive nephrectomy independent of IMDC risk category.
Authors: Daniel D. Shapiro, Jose A. Karam, Philippe E. Spiess, Jay D. Raman, Mary E. Westerman, Wade J. Sexton, Logan Zemp, Alyssa Bilotta, Glenn O. Allen, Kate V. Lauer, Surena F. Matin, Christopher G. Wood, E. Jason Abel
Journal: Journal of Clinical Oncology (2020)

652 Background: Studies suggest that overall survival (OS) following cytoreductive nephrectomy (CN) is associated with preoperative tumor measurements including primary tumor diameter, number of metastatic sites, sum of metastatic tumor diameters and primary tumor percent of overall burden. Current risk models, however, do not account for tumor burden. This study evaluated associations between OS and preoperative tumor measurements for patients treated with CN during the targeted therapy era. Methods: Data for consecutive mRCC patients treated with CN at 4 institutions from 2006-2017 were analyzed after determining IMDC risk category, primary tumor (PT) diameter, number of metastatic sites, sum of metastatic tumor diameters and PT percentage of overall burden. Univariate and multivariable (MV) Cox models evaluated tumor measurement and IMDC risk associations with OS. Results: A total of 617 patients were available for analysis. Median PT diameter was 10.0 cm (IQR 7-13cm), number of metastatic sites was 2 (IQR 1-2), sum of metastatic tumor diameters was 4.5 cm (IQR 2-10cm) and PT percent of overall burden was 73.7% (IQR 60-85%). After univariate analysis, all 4 tumor burden measures were associated with OS (p≤0.001 for all). MV models evaluating IMDC risk category with individual tumor burden measurements demonstrated that all measures were predictive as continuous variables: PT diameter (HR 1.03, 95% CI 1.01-1.06, p=0.007), sum of metastatic tumor diameters (HR 1.04, 95% CI 1.02-1.05, p&lt;0.001), PT percent of overall burden (HR 0.43, 95% CI 0.27-0.68, p&lt;0.001), and number of metastatic sites (HR 1.52, 95% CI 1.25-1.85, p&lt;0.001). Additional MV models were created using clinically significant tumor measurement cutoffs and IMDC risk groups. OS was independently associated with IMDC intermediate (HR 3.17, 95% CI 1.84-5.44, p&lt;0.001) and poor risk (HR 3.85, 95% CI 2.21-6.70, p&lt;0.001), PT percentage of overall burden &lt;90% (HR 1.41, 95% CI 1.05-1.89, p=0.021), and &gt;2 metastatic sites (HR 1.60, 95% CI 1.29-2.00, p&lt;0.001). Conclusions: PT and metastatic disease burden are independently associated with OS following CN. Future risk models should include tumor burden measurements.
Effect of Indoor Climate on Allergen Levels and Microorganism-Associated Molecular Patterns
Authors: Mehtap Haktanir Abul, Jonathan Gaffin, Na Guo, Nerwali Metwali, Marissa Hauptman, Peter Thorne, Diane Gold, Gary Adamkiewicz, Susan Redline, Wanda Phipatanakul
Journal: Journal of Allergy and Clinical Immunology (2020)