tbuckley/cabot-search huggingface dataset:
Abstract 1016: A new biomarker in hematological malignancies
Authors: Theo Borgovan
Journal: Cancer Research (2021)

Abstract Background: Extracellular vesicles (EVs) are biologically active nanoparticles. EVs from explant prostate cancer induce a neoplastic phenotype in normal prostate cell lines. We have also shown EVs from mesenchymal stem cells (MSC) can have a healing effect, reversing the malignant phenotype in prostate and colorectal cancer; as well as mitigating radiation damage to marrow. The role of EVs in leukemia and its microenvironment remains to be studied, and may provide insight for therapeutic advances. We hypothesize that EVs derived from normal MSC can have a healing effect, inhibiting the growth of myelogenous leukemia. Methods: Kasumi AML cells lines were seeded in a 96 well plate with various concentrations of MSC-derived EVs. Vesicles were isolated usingan established differential centrifugation technique, and were co-cultured with Kasumi. To study cellular proliferation we measured fluorescence after 60 min. Fluorescence intensities were normalized to control wells containing non-EV treated cells alone. Results: Proliferation of AML cells after one day of co-culture with MSC-EVs respectively was inhibited in a dose dependent manner. Three days of co-culture with similar doses resulted in ~40% and ~80%reduction in proliferation when normalized to control. At day 6 of co-culture growth was inhibited by ~80% at both EV concentrations when normalized to control. Summary/Conclusion: MSC-derived EVs inhibits the growth of the AMLcell line in vitro. This effect is seen as early as 1 day of co-culture andpersists out to 3, and 6 days implicating an miRNA-mediated mechanismthat has been discussed in previous works. We feel this is perhaps a modelof how a normal marrow works to suppress early cancer.As leukemia develops the cross-talk between AML and its microenvironmentalters the MSCs to promote a survival signal favouring AMLgrowth. Future work involves the capacity of AML-derived EVs to alterthe phenotype of normal marrow towards a pro-leuekmic phenotype.Employing mathematical models to quantify and ultimately predict thesechanges allows for precise therapeutic intervention. Citation Format: Theo Borgovan. A new biomarker in hematological malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1016.
Abstract 2838: Epigenetic regulator MLL3 mutations promote tumor metastasis by enhancing the epithelial-mesenchymal transition state
Authors: Jihong Cui, Kai Ge, Wenjun Guo
Journal: Cancer Research (2021)

Abstract Epigenetic dysregulations have a recognized role in cancer pathogenesis. Histone methyltransferase MLL3 (mixed-lineage leukemia protein 3) (gene symbol - KMT2C) is one of the most frequently altered genes in human breast cancer. In addition to the loss-of-function mutations, the expression levels of MLL3 are downregulated significantly in the tumor, compared to normal breast samples. Consistent with these cancer genome findings, functional studies in mouse models and human cancer cells showed loss of MLL3 promotes tumor initiation and growth. However, the role of MLL3 mutation in metastasis has not been determined. Here we showed that the MLL3 levels were further reduced in distant metastases compared to primary tumors, suggesting a potential role of MLL3 loss in metastasis. We demonstrate that MLL3 loss markedly promoted distant metastasis through specifically enhancing the step of colonization during the metastatic cascade. MLL3 loss facilitated the acquisition of an epithelial/mesenchymal (E/M) transition state by cancer cells disseminated to the lung. These cells have a hybrid phenotype of epithelial and mesenchymal features. We further showed that the E/M transitional cells induced by MLL3 loss have greatly increased tumor-initiating ability and multi-organ metastatic ability. We further demonstrated that MLL3 lose facilitated luminal breast tumor cells to acquire the E/M hybrid features and promoted endocrine therapy resistance, suggesting that loss of MLL3 also promotes the epithelial-mesenchymal plasticity and therapeutic resistance. To identify vulnerability of MLL3-mutant cancer cells, we performed small molecule screening and discovered that MLL3-mutant cancer cells are markedly more sensitive to BET inhibitors than MLL3-WT cells. The in vivo study confirmed that the BET inhibitor repressed the MLL3-mutant tumor growth much more efficiently than MLL3-WT tumors. Furthermore, the BET inhibitor is effective in suppressing the growth of established MLL3-mutant lung metastasis. Taken together, our findings indicate that MLL3 mutations promotes metastasis and therapeutic resistance by enhancing epithelial-mesenchymal plasticity. However, these aggressive cancer cells are uniquely vulnerable to BET inhibition, suggesting a potential therapeutic strategy for MLL3-mutant cancers. Citation Format: Jihong Cui, Kai Ge, Wenjun Guo. Epigenetic regulator MLL3 mutations promote tumor metastasis by enhancing the epithelial-mesenchymal transition state [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2838.
Abstract 2862: BMP4 mediated suppression of cholesterol synthesis and breast cancer metastasis
Authors: Robin L. Anderson, Lap Hing Chi, Allan D. Burrows, Suraya Roslan, Andrew Redfern
Journal: Cancer Research (2021)

Abstract Breast cancer affects one in seven women and kills more than 600,000 women each year. Compared to the 98.9% survival rate of patients with localized breast cancer, the five-year survival rate of patients with distant metastasis is only 28.1%. Using cDNA arrays and patient datasets, we found that a protein called bone morphogenetic protein 4 (BMP4) is downregulated in highly metastatic breast cancer cells and in high-grade breast tumors. BMP4 is a ligand in the TFGβ/BMP cytokine family and has the capacity to suppress TGFβ signaling through induction of SMAD6 and SMAD7. In several different preclinical metastasis models, we have shown that restored BMP4 expression in breast cancer cells with metastatic capacity does not alter primary tumor growth but results in significantly reduced metastasis to lung, liver and spine (p&amp;lt; 0.01), following primary tumor resection. MDA-MB-231HM cells with or without enforced BMP4 expression were recovered from primary mammary tumors and subjected to transcriptomic profiling by RNAseq. This analysis revealed that BMP4 suppressed multiple genes involved in the cholesterol biosynthesis pathway (p=2.56×10-7) and down-regulated cholesterol levels in the tumors (p=0.042). In a patient cohort of over 2000 predominantly luminal breast cancers, we found that stage, as measured by size and lymph node status, was not altered by statin use, however statin users had less high grade tumors and more luminal A tumors. In terms of recurrence, we found a marked risk reduction in patients with luminal B tumors (p=0.014) and particularly in Her2+ luminal B tumors (p=0.045). Lung, liver and brain metastases were most reduced in statin users. Current experiments involve testing a statin therapy, with the knowledge that statins are not effective in mice, but should inhibit cholesterol synthesis in human tumors in xenograft models. In addition, we are testing an inhibitor of the nuclear receptor RORγ that has been reported to activate cholesterol synthesis through SREBP2, a master regulator of cholesterol synthesis. Citation Format: Robin L. Anderson, Lap Hing Chi, Allan D. Burrows, Suraya Roslan, Andrew Redfern. BMP4 mediated suppression of cholesterol synthesis and breast cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2862.
Diagnostic accuracy of PSMA-PET-CT for pelvic lymph node staging in men with prostate cancer undergoing radical prostatectomy and pelvic lymph node dissection
Authors: J.B. Grogg, A. Affentranger, M.S. Wettstein, B. Kaufmann, N.C. Grossmann, D. Eberli, C. Poyet, T. Hermanns, C.D. Fankhauser
Journal: European Urology (2021)
Application of deep learning convolutional neural network in prediction of stone location, skin to stone distance and composition in renal lithiasis: A single center pilot study
Authors: B.M. Zeeshan Hameed, B. Somani, N. Naik, A. Talasila, M. Shah, S. Reddy, G. Sachdev, R. Hussein Beary, P. Hegde
Journal: European Urology (2021)
MRI-Targeted or Standard Biopsy in Prostate Cancer Screening
Authors: Martin Eklund, Fredrik Jäderling, Andrea Discacciati, Martin Bergman, Magnus Annerstedt, Markus Aly, Axel Glaessgen, Stefan Carlsson, Henrik Grönberg, Tobias Nordström
Journal: New England Journal of Medicine (2021)

High rates of overdiagnosis are a critical barrier to organized prostate cancer screening. Magnetic resonance imaging (MRI) with targeted biopsy has shown the potential to address this challenge, but the implications of its use in the context of organized prostate cancer screening are unknown.We conducted a population-based noninferiority trial of prostate cancer screening in which men 50 to 74 years of age from the general population were invited by mail to participate; participants with prostate-specific antigen (PSA) levels of 3 ng per milliliter or higher were randomly assigned, in a 2:3 ratio, to undergo a standard biopsy (standard biopsy group) or to undergo MRI, with targeted and standard biopsy if the MRI results suggested prostate cancer (experimental biopsy group). The primary outcome was the proportion of men in the intention-to-treat population in whom clinically significant cancer (Gleason score ≥7) was diagnosed. A key secondary outcome was the detection of clinically insignificant cancers (Gleason score 6).Of 12,750 men enrolled, 1532 had PSA levels of 3 ng per milliliter or higher and were randomly assigned to undergo biopsy: 603 were assigned to the standard biopsy group and 929 to the experimental biopsy group. In the intention-to-treat analysis, clinically significant cancer was diagnosed in 192 men (21%) in the experimental biopsy group, as compared with 106 men (18%) in the standard biopsy group (difference, 3 percentage points; 95% confidence interval [CI], -1 to 7; P<0.001 for noninferiority). The percentage of clinically insignificant cancers was lower in the experimental biopsy group than in the standard biopsy group (4% [41 participants] vs. 12% [73 participants]; difference, -8 percentage points; 95% CI, -11 to -5).MRI with targeted and standard biopsy in men with MRI results suggestive of prostate cancer was noninferior to standard biopsy for detecting clinically significant prostate cancer in a population-based screening-by-invitation trial and resulted in less detection of clinically insignificant cancer. (Funded by the Swedish Research Council and others; STHLM3-MRI ClinicalTrials.gov number, NCT03377881.).
トロンボポエチンによるインターフェロン誘導性遺伝子ファミリー9-27中の一つの発現誘導:トロンボポエチンの作用分析
Authors: Fujimoto T, Katsutani S, Fujii T, Kimura A, Miyazaki H, Fujimura K
Journal: Blood (1996)
Abstract SY24-01: Spatiotemporal definitions of immune archetypes across cancer types
Authors: Matthew F. Krummel
Journal: Cancer Research (2021)

Abstract Cancers display significant heterogeneity with respect to tissue of origin, driver mutations and other features of the surrounding tissue. It is likely that persistent tumors differentially engage inherent patterns-here "Archetypes"-of the immune system, to both benefit from the tumor immune microenvironment (TIME) and to disengage tumor-targeting. To discover dominant immune system archetypes across diverse cancer types, we processed in an unbiased way 364 individual tumors across 12 cancer indications using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained on cell sub compartments uncovered archetypes that exist across indications and are durable to increased granularity in higher dimensions. Immune composition-based archetypes differentiate tumors based upon the distribution of large unrelated collections of immune and tumor gene-expression patterns. Archetypes discovered this way also tie closely to well-established classifications of tumor biology. The resultant Immunoprofiler Initiative (IPI) resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune infiltration and provides a rational path forward to study cancer immunity and learn how to modulate these patterns to improve therapy. Citation Format: Matthew F. Krummel. Spatiotemporal definitions of immune archetypes across cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY24-01.
High-Ambient Air Pollution Exposure Among Never Smokers Versus Ever Smokers With Lung Cancer
Authors: Renelle Myers, Michael Brauer, Trevor Dummer, Sukhinder Atkar-Khattra, John Yee, Barbara Melosky, Cheryl Ho, Anna L. McGuire, Sophie Sun, Kyle Grant, Alexander Lee, Martha Lee, Weiran Yuchi, Martin Tammemagi, Stephen Lam
Journal: Journal of Thoracic Oncology (2021)

Air pollution may play an important role in the development of lung cancer in people who have never smoked, especially among East Asian women. The aim of this study was to compare cumulative ambient air pollution exposure between ever and never smokers with lung cancer.A consecutive case series of never and ever smokers with newly diagnosed lung cancer were compared regarding their sex, race, and outdoor and household air pollution exposure. Using individual residential history, cumulative exposure to outdoor particulate matter (PM2.5) in a period of 20 years was quantified with a high-spatial resolution global exposure model.Of the 1005 patients with lung cancer, 56% were females and 33% were never smokers. Compared with ever smokers with lung cancer, never smokers with lung cancer were significantly younger, more frequently Asian, less likely to have chronic obstructive pulmonary disease or a family history of lung cancer, and had higher exposure to outdoor PM2.5 but lower exposure to secondhand smoke. Multivariable logistic regression analysis revealed a significant association with never-smoking patients with lung cancer and being female (OR = 4.01, 95% confidence interval [CI]: 2.76-5.82, p < 0.001), being Asian (ORAsian versus non-Asian = 6.48, 95% CI: 4.42-9.50, p < 0.001), and having greater exposure to air pollution (ORln_PM2.5 = 1.79, 95% CI: 1.10-7.2.90, p = 0.019).Compared with ever-smoking patients with lung cancer, never-smoking patients had strong associations with being female, being Asian, and having air pollution exposures. Our results suggest that incorporation of cumulative exposure to ambient air pollutants be considered when assessing lung cancer risk in combination with traditional risk factors.
Surgical quality, antihypertensive therapy and electrolyte balance: A novel trifecta for evaluating outcomes of unilateral primary aldosteronism
Authors: U. Anceschi, M. Mormando, C. Fiori, O. Zappalà, B. De Concilio, A. Brassetti, A. Carrara, M.C. Ferriero, G. Tuderti, L. Misuraca, A.M. Bove, R. Mastroianni, M. Appetecchia, G. Tirone, F. Porpiglia, A. Celia, M. Gallucci, G. Simone
Journal: European Urology (2021)
Long-lasting ex-4-Loaded carbohydrate Polymeric PLGA NPs ameliorate cerebral ischemia/reperfusion injury through efficiently inhibiting oxidative stress, endoplasmic reticulum stress, apoptosis, autophagy and pyroptosis signaling in diabetic rats
Authors: C.Y. Chang, C-H. Chung, S-D. Chung, Y-H. Cheng, W-H. Wang, C-P. Yang, C-T. Chien
Journal: European Urology (2021)
DYRK1a mediates BAFF-induced noncanonical NF-κB activation to promote autoimmunity and B-cell leukemogenesis
Authors: Yanchuan Li, Xiaoping Xie, Zuliang Jie, Lele Zhu, Jin-Young Yang, Chun-Jung Ko, Tianxiao Gao, Antrix Jain, Sung Yun Jung, Natalia Baran, Marina Y. Konopleva, Xuhong Cheng, Shao-Cong Sun
Journal: Blood (2021)
Prognostic Significance of Plasmablastic Plasma Cells in the Era of Novel Agents in Multiple Myeloma
Authors: Antoine Machet, Stephanie Guidez, Guillemette Fouquet, Thomas Systchenko, Deborah Desmier, Niels Moya, Cécile Gruchet, Anthony Levy, Florence Sabirou, Arthur Bobin, Valentine Richez, Celine Dieval, Carine Motard, Florence Borde, Geraldine Durand, Isabelle Azais, Vincent Javaugue, Cecile Tomowiak, Sabrina Bouyer, Ouda Ghoual, Elodie Dindinaud, Frank Bridoux, Pieter Sonneveld, Herve avet Loiseau, Xavier Leleu
Journal: Blood (2017)
Technically simplified peroral endoscopic myotomy: blunt dissection making submucosal tunneling fast and safe
Authors: Xiao Hu, Ying-hui Zhang, Xiao-gang Liu, Sheng-xi Han, Wei-hui Liu
Journal: Endoscopy (2021)

As a primary treatment for patients with achalasia [1], peroral endoscopic myotomy (POEM) is a technically demanding procedure [2]. To perform a high-quality POEM and to prevent complications such as leakages, infections, major bleeding, and gas-related events, the establishment of a submucosal tunnel and the integrity of the mucosal flap are crucial [3] [4]. We present a blunt dissection technique to achieve rapid and safe submucosal tunneling in the aim to build a technically simplified POEM, which we call blunt POEM ([Video 1]).
Treatment of bladder prolaps by sacrocolpopexy with jaimy robotic system
Authors: G. Stoica, J. Lakssir, Y. Himmi, H. Dergamoun, C. Balsanu, T. Coroi, S. Regragui, P. Maulaz, H. Benhard, M.E. De Tinguy, M. Haydar
Journal: European Urology (2021)
Abstract 750: Race differences in telomere length in benign prostate and subsequent risk of prostate cancer
Authors: Benjamin A. Rybicki, Sudha M. Sadasivan, Yalei Chen, Ian Loveless, Nilesh S. Gupta, Dhananjay A. Chitale, Sean R. Williamson, Andrew G. Rundle, Deliang Tang
Journal: Cancer Research (2021)

Abstract Telomere shortening is linked to aging and thought to be associated with increased risk for cancer. Most cancer studies have used leukocyte telomere length as a surrogate measure for telomere length with few focused upon telomeres in the target tissue of cancer origin. To determine whether telomere length in pre-malignant prostate tissue is associated with subsequent prostate cancer risk, we conducted a case-control study of 530 case-control pairs matched on date, age at cohort entry, and race nested within a historical cohort of 10,478 men with a benign prostate biopsy. Overall mean telomere length assessed using modified quantitative real-time PCR was not different in benign prostate biopsies of prostate cancer cases vs. matched controls (1.65 ± 0.35 vs. 1.64 ± 0.39; p=0.41). However, race was significantly associated with telomere length with African American (AA) men having shorter telomeres in benign prostate biopsy compared with white men (1.59 ± 0.37 vs. 1.70 ± 0.37; p&amp;lt;0.0001). In race-stratified analyses, telomere length only showed a suggestive association with prostate cancer risk in white men, wherein those with telomere length in the highest quartile had 1.5-fold greater risk of prostate cancer compared to men with prostate telomere lengths in the lowest quartile (OR=1.56; 95% CI = 0.89 - 2.73 ). In addition, white men in the highest prostate telomere length quartile had almost three-fold greater risk of aggressive prostate cancer, defined as Gleason group 3 and above, tumor stage 3 or above or PSA 20 ng/ml or higher , compared with men with telomere lengths in the lowest quartile (OR=2.73; 95% CI =1.05 - 7.15). In summary, white men have longer telomeres in benign prostate tissue compared with AA men, and those with the longest telomeres may be at increased risk for prostate cancer, particularly the more aggressive form of the disease. Citation Format: Benjamin A. Rybicki, Sudha M. Sadasivan, Yalei Chen, Ian Loveless, Nilesh S. Gupta, Dhananjay A. Chitale, Sean R. Williamson, Andrew G. Rundle, Deliang Tang. Race differences in telomere length in benign prostate and subsequent risk of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 750.
Common elective orthopaedic procedures and their clinical effectiveness: umbrella review of level 1 evidence
Authors: Ashley W Blom, Richard L Donovan, Andrew D Beswick, Michael R Whitehouse, Setor K Kunutsor
Journal: BMJ (2021)

To determine the clinical effectiveness of common elective orthopaedic procedures compared with no treatment, placebo, or non-operative care and assess the impact on clinical guidelines.Umbrella review of meta-analyses of randomised controlled trials or other study designs in the absence of meta-analyses of randomised controlled trials.Ten of the most common elective orthopaedic procedures-arthroscopic anterior cruciate ligament reconstruction, arthroscopic meniscal repair of the knee, arthroscopic partial meniscectomy of the knee, arthroscopic rotator cuff repair, arthroscopic subacromial decompression, carpal tunnel decompression, lumbar spine decompression, lumbar spine fusion, total hip replacement, and total knee replacement-were studied. Medline, Embase, Cochrane Library, and bibliographies were searched until September 2020.Meta-analyses of randomised controlled trials (or in the absence of meta-analysis other study designs) that compared the clinical effectiveness of any of the 10 orthopaedic procedures with no treatment, placebo, or non-operative care.Summary data were extracted by two independent investigators, and a consensus was reached with the involvement of a third. The methodological quality of each meta-analysis was assessed using the Assessment of Multiple Systematic Reviews instrument. The Jadad decision algorithm was used to ascertain which meta-analysis represented the best evidence. The National Institute for Health and Care Excellence Evidence search was used to check whether recommendations for each procedure reflected the body of evidence.Quality and quantity of evidence behind common elective orthopaedic interventions and comparisons with the strength of recommendations in relevant national clinical guidelines.Randomised controlled trial evidence supports the superiority of carpal tunnel decompression and total knee replacement over non-operative care. No randomised controlled trials specifically compared total hip replacement or meniscal repair with non-operative care. Trial evidence for the other six procedures showed no benefit over non-operative care.Although they may be effective overall or in certain subgroups, no strong, high quality evidence base shows that many commonly performed elective orthopaedic procedures are more effective than non-operative alternatives. Despite the lack of strong evidence, some of these procedures are still recommended by national guidelines in certain situations.PROSPERO CRD42018115917.