tbuckley/cabot-search huggingface dataset:
Abstract 1479: Pan-cancer efficacy of BRAF and/or MEK inhibitors in BRAF V600-mutant multiple non-melanoma cancers: A clinico-genomic study
Authors: Jacob J. Adashek, Aakash P. Desai, Arjun K. Menta, Jason Roszik, Vivek Subbiah
Journal: Cancer Research (2021)

Abstract Background: BRAF and MEK inhibitors are currently FDA approved for melanoma, non-small cell lung cancer, and anaplastic thyroid cancer. The lack of clinical benefit with BRAF inhibition in BRAF V600+ colorectal cancer (CRC) has prevented its tissue-agnostic drug development. However, updated results from Vemurafenib-Basket study (Cancer Discov. 2020 May;10(5):657-663 ) and the NCI-match trial ( J Clin Oncol. 2020 Nov 20;38(33):3895-3904) reveal that BRAF pathway inhibition is active in &amp;gt; 20 unique cancer types. Objective: We aimed to describe the characteristics of BRAF V600 and study real-world outcomes using a clinico-genomic analysis using the AACR Genie database and the current medical literature. Methods: We reviewed the AACR GENIE database for the prevalence of BRAF V600 mutations across tumor types. We conducted a literature search (using PubMed from 2012-2019) for case reports of clinical response and outcomes in patients with BRAF V600 mutation-positive non-melanoma cancers who received BRAF inhibitor therapy. Results: Among 96,324 samples, BRAF V600 mutations were seen in 43 different tumor types across 2,963 samples (3.07 %) in the AACR GENIE database. BRAF V600 was most commonly present in thyroid cancer (40.9%), parathyroid cancer (31.8%), melanoma (26.1%), histiocytosis (25.7%), and head and neck NOS (14.3%). Literature review revealed total of 178 cases across 69 tumor types. The most common cases included Erdheim-Chester disease (n = 30, 16.9%), papillary thyroid carcinoma (n=16, 8.9%), anaplastic thyroid carcinoma (n = 13, 7.3%), and hairy cell leukemia (n = 13, 7.3%). Furthermore, dabrafenib (BRAF), dabrafenib/trametinib (BRAF+MEK), trametinib(MEK), vemurafenib (BRAF), vemurafenib/trametinib (BRAF+MEK), vemurafenib/cobimetinib (BRAF+MEK) were used in 34% (n =56), 16% (n = 27), 4% (n = 6), 44% (n = 72), 1% (n = 1), 2% (n =3), respectively. Overall, median PFS was 6.5 months, and median OS was 28.5 months with a median duration of response (DOR) of 8 months. Conclusion: BRAF V600 mutations are prevalent across multiple non-melanoma cancers, lead to oncogene addiction and are clinically actionable in a broad range of non-melanoma cancers. Continued drug development is warranted beyond the current BRAF+/- MEK approved cancers. Citation Format: Jacob J. Adashek, Aakash P. Desai, Arjun K. Menta, Jason Roszik, Vivek Subbiah. Pan-cancer efficacy of BRAF and/or MEK inhibitors in BRAF V600-mutant multiple non-melanoma cancers: A clinico-genomic study [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 1479.
Eligibility for focal treatment of ISUP grade 2 single lesion on MRI-targeted biopsies
Authors: A.S. Bajeot, S. Albisinni, T. Roumeguère, G. Fiard, M. Lesourd, C. Manceau, A. Salin, G. Loison, N. Doumerc, M. Thoulouzan, C. Tollon, C. Almeras, J-R. Gautier, X. Gamé, M. Soulié, J-B. Beauval, R. Diamand, G. Ploussard, M. Roumiguié
Journal: European Urology (2021)
Trileucine as a dispersibility enhancer of spray-dried inhalable microparticles
Authors: Mani Ordoubadi, Florence K.A. Gregson, Hui Wang, Nicholas B. Carrigy, Mark Nicholas, Sandra Gracin, David Lechuga-Ballesteros, Jonathan P. Reid, Warren H. Finlay, Reinhard Vehring
Journal: Journal of Controlled Release (2021)
Characterization of immunological status in the thymoma patients after thymectomy
Authors: Eva Zavadova, Eva Sedla, kova, Lubos Petruzelka, Terezie Fu, ikova, Ivan Sterzl
Journal: Cancer Research (2008)

267  Paraneoplastic immunity disorders are more common in patients withthymomas. Around 30% of all thymoma patients develop myastenia gravis. Frequently, patients suffer under recurrent respiratory tract infections. Thymectomy does not always improve the patient9s condition,.  The pathogenesis is still not entirely understood, but changes in the immune response and the cytokines production are the most frequently discussed as the reason of the recurrent infections in thymoma patients.  AIM: To find out the changes in the parameters of the cellular and humoral immunity including cytokines production (IFN gamma, TNF alpha, IL2, IL -4, IL-10and IL-12 )in patitents after thymectomy .  MATERIALS AND METHODS: Eleven patients were analyzed 6 months to 10 years after thymectomy due to thymoma. ELISA and flow cytometry techniques were used to evaluate the immunological status of the subjects. Patients with immundeficience were treated with substitution of immunoglobulins.  RESULTS: 8 subjects suffered from myasthenia gravis, and recurrent infections of upper and lower respiratory tract appeared in 6 patients. The immunological analyses revealed the changes in IgG level in 6 patients, decrease was mainly in the IgG1subgroup. On contrary, IgA was enhanced in 7 patients. There were no changes in ECP, C3 and C4 as well. Thymoma patients showed also anemia in 2 cases and lymfopenia (5 patients).All 11 patients showed enhanced monocytes percentage in peripheral blood. Autoantibodies were presented in all patients. The percentages of CD4+ and CD8+ T lymphocytes and CD 19 was lower in 3 patients, but the CD4:CD8 ratio was changed in 8 from 11 thymectomized patients as compared with the healthy controls. 7 patiens showed high TNF as well as IFN gamma production., IL-10 was elevated in 2 patients. IL12 was decreased in 6 patients,.There were no changes in IL-4 production .Administration of immunoglobulins led to reduction of respiratory tract infections.  CONCLUSIONS: Recurrent infections may be the first symptoms of immunological disturbances after thymectomy in adults. In our study, thymoma patients with recurrent infections showed imbalance of immune responses associated with disturbed cytokine production. It is suggested that regular medical monitoring and immunoglobulin replacement in these patients is important in preventing further complications, which may result in irreversible lung tissue destruction.
Practice Patterns and Outcomes of Novel Targeted Agents for the Treatment of <i>ERBB2</i>-Positive Metastatic Breast Cancer
Authors: Josee-Lyne Ethier, Danielle Desautels, Andrew Robinson, Eitan Amir, Weidong Kong, Christopher M. Booth
Journal: JAMA Oncology (2021)

Clinical trials have shown that the addition of pertuzumab to trastuzumab-based chemotherapy for first-line treatment of ERBB2-positive metastatic breast cancer is associated with considerable improvement in overall survival (OS). In the second-line setting, trastuzumab emtansine (T-DM1) improves OS compared with capecitabine/lapatinib in patients previously treated with trastuzumab-based chemotherapy. However, there are few data describing long-term real-world outcomes with these agents. To describe practice patterns and outcomes associated with pertuzumab and T-DM1 in routine clinical practice. This population-based retrospective cohort study used the Ontario Cancer Registry linked to electronic treatment databases to identify all patients treated with pertuzumab and T-DM1 following reimbursement approval in Ontario, Canada, which has a single-payer public health system. Participants included women with stage IV ERBB2-positive metastatic breast cancer receiving treatment with pertuzumab for first-line metastatic indication from December 2013 through December 2017, and those treated with T-DM1 from May 2014 through December 2017. Pertuzumab and T-DM1 cohorts were analyzed separately. Data were analyzed December 2019 to December 2020. Treatment with pertuzumab or T-DM1. The primary outcome was OS, determined using the Kaplan-Meier method. Factors associated with OS were identified using a Cox proportional hazard model. The median (interquartile range [IQR]) age of the 795 women who received pertuzumab and 506 women who received T-DM1 was 57 (49-67) and 56 (48-66) years, respectively. Among the cohort of patients who received pertuzumab, the median (IQR) OS and time on treatment was 43 (16.2-unavailable) and 14 (6.0-26.2) months, respectively. In the T-DM1 cohort, the proportion of pertuzumab-naive patients decreased over time from 68 of 91 [74.7%] in 2014 to 16 of 89 [18.0%] in 2017 (P < .001). The median (IQR) OS and time on treatment was 15 (6.7-27.7) and 4 (1.4-9.0) months, respectively. Median OS was shorter for patients with prior pertuzumab treatment than in the pertuzumab-naive subgroup (12 vs 19 months; adjusted hazard ratio, 0.70; 95% CI, 0.55-0.89; P = .004). In this population-based cohort study, the survival of patients treated with pertuzumab and T-DM1 in routine practice appeared inferior to results from pivotal clinical trials. Differences in outcome likely reflect differences in patient population and previous lines of therapy in routine practice. Further work is needed to understand the effectiveness of T-DM1 after pertuzumab exposure.
Aspects of high-performance and bio-acceptable magnetic nanoparticles for biomedical application
Authors: Preeti Kush, Parveen Kumar, Ranjit Singh, Ajeet Kaushik
Journal: Asian Journal of Pharmaceutical Sciences (2021)

This review covers extensively the synthesis & surface modification, characterization, and application of magnetic nanoparticles. For biomedical applications, consideration should be given to factors such as design strategies, the synthesis process, coating, and surface passivation. The synthesis method regulates post-synthetic change and specific applications in vitro and in vivo imaging/diagnosis and pharmacotherapy/administration. Special insights have been provided on biodistribution, pharmacokinetics, and toxicity in a living system, which is imperative for their wider application in biology. These nanoparticles can be decorated with multiple contrast agents and thus can also be used as a probe for multi-mode imaging or double/triple imaging, for example, MRI-CT, MRI-PET. Similarly loading with different drug molecules/dye/fluorescent molecules and integration with other carriers have found application not only in locating these particles in vivo but simultaneously target drug delivery/hyperthermia inside the body. Studies are underway to collect the potential of these magnetically driven nanoparticles in various scientific fields such as particle interaction, heat conduction, imaging, and magnetism. Surely, this comprehensive data will help in the further development of advanced techniques for theranostics based on high-performance magnetic nanoparticles and will lead this research area in a new sustainable direction.
Partial nephrectomy in frail patients: Effect of surgical approach on complications and health-care expenditures
Authors: G. Rosiello, G. Fallara, A. Martini, D. Cignoli, G. Basile, G. Colandrea, G. Baiamonte, D. Canibus, F. Trevisani, A. Bettiga, Z. Tian, A. Kapoor, S.F. Shariat, C. Giancristofaro, M. Romani, A. Briganti, F. Montorsi, A. Salonia, P. Karakiewicz, A. Larcher, U. Capitanio
Journal: European Urology (2021)
Abstract 126: HUB Organoids: bringing the 'patient in the lab' for preclinical and clinical development
Authors: Jasper Mullenders, Annemarie Buijs, Lars-Eric Fielmich, Jasper Sluimer, Jane Sun, Robert G. Vries, Sylvia F. Boj
Journal: Cancer Research (2021)

Abstract Preclinical disease models are essential for the development of novel therapies and help better understand the molecular processes. In recent years, the groundbreaking technology to generate patient specific in vitro cultures based on adult stem-cell (ASC) organoids, has gained widespread interest for the development of new therapies and as a predictive diagnostic tool. ASC-derived organoids can be generated at high efficiency from both healthy and diseased tissue (resections as well as biopsies) including most carcinomas. These patient-derived cultures can be expanded for prolonged periods of time while maintaining many properties of the tissue they were derived from. At Hubrecht Organoid Technology (HUB), we have created comprehensive ‘organoid living biobanks' from tumors of different origin like colon, lung, breast, pancreas and ovary. These biobanks have been characterized at the genetic and transcriptional level. These analyses have shown that our ‘organoid living biobanks' capture disease heterogeneity at the genetic and molecular level. Because HUB Organoids can be expanded long term, drug screening is feasible in these models. HUB has developed procedures for (high-throughput) compound screening in organoids including small molecules and biologics. In this setting, HUB Organoids have been used to identify novel targets, identify lead compounds and stratify potential responders based on their genetic or molecular profile. In addition, HUB Organoids can serve as a patient avatar in clinical development or diagnostics. In this setting, HUB Organoids could add a functional test for therapy response in a patient centered setting providing a unique tool for personalized medicine. Citation Format: Jasper Mullenders, Annemarie Buijs, Lars-Eric Fielmich, Jasper Sluimer, Jane Sun, Robert G. Vries, Sylvia F. Boj. HUB Organoids: bringing the 'patient in the lab' for preclinical and clinical development [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 126.
Non-terminally exhausted tumor-resident memory HBV-specific T cell responses correlate with relapse-free survival in hepatocellular carcinoma
Authors: Yang Cheng, Bavani Gunasegaran, Harsimran D. Singh, Charles-Antoine Dutertre, Chiew Yee Loh, Jia Qi Lim, Jeremy Chase Crawford, Hong Kai Lee, Xiaomeng Zhang, Bernett Lee, Etienne Becht, Wan Jun Lim, Joe Yeong, Chung Yip Chan, Alexander Chung, Brian K.P. Goh, Pierce K.H. Chow, Jerry K.Y. Chan, Florent Ginhoux, David Tai, Jinmiao Chen, Seng Gee Lim, Weiwei Zhai, Su Pin Choo, Evan W. Newell
Journal: Immunity (2021)
Evaluation of oncological outcomes and data quality in studies assessing nerve sparing versus non-nerve sparing radical prostatectomy in non-metastatic prostate cancer: A systematic review
Authors: L. Moris, G. Gandaglia, A. Vilaseca, T. Van Den Broeck, E. Briers, M. De Santis, S. Gillessen, N. Grivas, A. Henry, T.B. Lam, M. Lardas, M. Mason, D. Oprea-Lager, G. Ploussard, O. Rouvière, I.G. Schoots, H. Van Der Poel, T. Wiegel, P-P. Willemse, J.P. Grummet, D. Tilke, R.C.N. Van Den Bergh, P. Cornford, N. Mottet
Journal: European Urology (2021)
Abstract 341: Predicting clinical endocrine response in advanced breast cancers using a reproducible low-dimensional biomarker
Authors: Aritro Nath, Adam Cohen, Jeffrey Chang, Andrea Bild
Journal: Cancer Research (2021)

Abstract In the absence of reliable and effective prognostic biomarkers, endocrine therapy remains the standard of care for all advanced and metastatic estrogen receptor-positive (ER+) breast cancers. Attempts to develop biomarkers using the baseline tumor transcriptome or genome of advanced ER+ breast cancers have so far been unsuccessful due to predictive models with poor reproducibility in independent studies. Here we present an approach to develop a low-dimensional biomarker that estimates the risk of adverse events on endocrine therapy using the baseline tumor transcriptome of patients. Using a framework for supervised dimensionality reduction of the gene expression feature space, we constructed an endocrine response signature (ENDORSE) modeled on the survival outcomes of ER+ breast cancers from METABRIC. ENDORSE outperformed transcriptome-wide and knowledge-based signature models while significantly improving upon routine histopathological and genomic classifiers in cross-validation analyses. The ENDORSE risk estimate accurately predicted the outcomes for endocrine therapy in three independent clinical trials for ER+ breast cancers. Further, analysis of the phenotypes enriched in high-risk categories show endocrine resistance was not associated with rates of proliferation, but instead with a potential loss of DNA damage repair and cell-matrix interaction pathways. Citation Format: Aritro Nath, Adam Cohen, Jeffrey Chang, Andrea Bild. Predicting clinical endocrine response in advanced breast cancers using a reproducible low-dimensional biomarker [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 341.
Immune Profiling Mass Cytometry Assay Harmonization: Multicenter Experience from CIMAC-CIDC
Authors: Bita Sahaf, Mina Pichavant, Brian H. Lee, Caroline Duault, Emily M. Thrash, Melanie Davila, Nicolas Fernandez, Karen Millerchip, Salah-Eddine Bentebibel, Cara Haymaker, Natalia Sigal, Diane M. Del Valle, Srinika Ranasinghe, Sarah Fayle, Beatriz Sanchez-Espiridion, Jiexin Zhang, Chantale Bernatchez, Catherine J. Wu, Ignacio I. Wistuba, Seunghee Kim-Schulze, Sacha Gnjatic, Sean C. Bendall, Minkyung Song, Magdalena Thurin, J. Jack Lee, Holden T. Maecker, Adeeb Rahman
Journal: Clinical Cancer Research (2021)

The Cancer Immune Monitoring and Analysis Centers - Cancer Immunologic Data Commons (CIMAC-CIDC) Network is supported by the NCI to identify biomarkers of response to cancer immunotherapies across clinical trials using state-of-the-art assays. A primary platform for CIMAC-CIDC studies is cytometry by time of flight (CyTOF), performed at all CIMAC laboratories. To ensure the ability to generate comparable CyTOF data across labs, a multistep cross-site harmonization effort was undertaken.
Abstract 15469: The Efficacy and Safety of Atrial Fibrillation Ablation in the VA Healthcare System
Authors: Akshay Goel, Fuad Habash, Zaid Gheith, Bilal Alqam, Khaldia Khaled, Amjad Abualsuod, Mohammed E Madmani, Srikanth Vallurupalli, Waddah Maskoun
Journal: Circulation (2018)

Introduction: Atrial fibrillation (AF) is associated with adverse outcomes such as increased healthcare costs, impaired quality of life (QOL), stroke and mortality. Catheter ablation of AF plays an...
Ceftriaxone-induced disruption of oxalate homeostasis is associated with total fecal microbiota oxalate-degrading activity but not with the numbers of oxalate-degrading bacteria in the experimental rats
Authors: I. Akulenko, G. Tolstanova, N. Stepanova, T. Sergeiychuk, S. Savchenko, M. Kolesnyk
Journal: European Urology (2021)
A Mimic of Myocardial Ischemia in a Woman With Hyperemesis Gravidarum
Authors: Nisha N. Menon
Journal: JAMA Internal Medicine (2021)

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Abstract 2679: Role of TH2 cells in pancreatic cancer progression
Authors: Aftab Alam, Maulasri Bhatta, Parker Denz, Eric Levanduski, Prasenjit Dey
Journal: Cancer Research (2021)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that remains largely incurable. Although the cause for this profound therapeutic resistance is poorly understood, it is however partly blamed on signaling factors present in the tumor microenvironment (TME), which supports the proliferation and survival of neoplastic cells. Apart from being stroma rich, PDAC TME is associated with a distinctive tumor immune infiltrate. Paradoxically, most immunotherapy trials using immune checkpoint inhibitors, either as monotherapy or combination, failed to increase patient survival motivating exploration of new therapeutic strategies. To that end, the cytokine mediated heterotypic interactions between cancer cells and immune cells remain largely unexplored. Here, we explored the role of oncogenic Kras (KrasG12D=Kras*) in pro-tumorigenic signaling interactions between cancer cells and host cells. We found that TH2 cells infiltrate the pancreas in the early stage of the tumorigenesis and secrete type 2 cytokines [interleukin (IL)4 and IL13]. Further, Kras* signaling is involved in establishing this paracrine circuit utilizing type 2 cytokines in the PDAC tumor microenvironment (TME)2. Integrated transcriptomic, chromatin occupancy and metabolomic studies identified cMyc, as a direct target of activated Stat6, and that cMyc drives glycolysis. Thus, paracrine signaling in the tumor microenvironment plays a key role in the Kras*-driven metabolic reprogramming of PDAC. This study and the work of others expanded the role of immune cell derived cytokines in the context of Kras* driven PDAC through its promotion of cancer cell proliferation. Importantly, perturbation of the IL4 and/or IL13 mediated signaling restricts tumor growth and increases survival in a mouse model of PDAC. Notably, PDAC patients with predominantly TH2 (Gata3+) polarized lymphoid cell infiltration show reduced survival compared to tumors with higher TH1 (Tbet+) cells. Finally, the presence of TH2 cells in the PDAC TME might explain the immense immunotherapy resistance observed in PDAC patients and anti-TH2 treatment might sensitize these patients to immune checkpoint inhibitors. Our subsequent preliminary work identified a potent inflammatory cytokine, IL33 which is overexpressed and released by PDAC cells that attract and activate TH2 and other immune cells such as Tregs. Inhibition of IL33 leads to a decrease in the infiltration and activation of TH2 cells and Treg cells, accompanied by significant PDAC tumor regression. Citation Format: Aftab Alam, Maulasri Bhatta, Parker Denz, Eric Levanduski, Prasenjit Dey. Role of TH2 cells in pancreatic cancer progression [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 2679.