tbuckley/cabot-search huggingface dataset:
Abstract 2409: The regulation of mitochondria metabolism is correlated with gemcitabine resistance in MIA-PaCa-2 cell line
Authors: Rina Fujiwara-Tani, Shingo Kishi, Shiori Mori, Hiroki Kuniyasu
Journal: Cancer Research (2021)

Abstract We established gemcitabine (GEM)-resistant pancreatic ductal adenocarcinoma (PDAC) cell line, MIA-G cells from MIA-PaCa-2 (MIA-P) cells by continuous low-dose GEM treatment. MIA-G cells was also resistant to 5-fluorouracil in comparison with MIA-P. Metabolic flux analysis showed that oxygen consumption rate (OCR) in MIA-G cells was higher than MIA-P cells, however, OCR was suppressed by GEM treatment only in MIA-G cells. In MIA-P cells, GEM treatment generated elevation of mitochondrial membrane potential and mitochondrial ROS, but not MIA-G cells. In MIA-G cells, expression of mitochondrial transcription factor A was also decreased. Moreover, glutamine uptake and glutamine peroxidase level were elevated in MIA-G cells. These findings suggest that suppression of OXPHOS contributes to GEM resistance through reduction of ROS production. Citation Format: Rina Fujiwara-Tani, Shingo Kishi, Shiori Mori, Hiroki Kuniyasu. The regulation of mitochondria metabolism is correlated with gemcitabine resistance in MIA-PaCa-2 cell line [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 2409.
Abstract 2177: Tumor neoantigen profiling with validated patient-specific TCR characterization to improve neoepitope prediction
Authors: Zheng Pan, Olivier Dalmas, Songming Peng, Kyle Jacoby, Barbara Sennino, Yan Ma, Chad Smith, Amin Momin, Allison Xu, Katharine Heeringa, Jonathan Johnston, Duo An, Boi Quach, William Lu, Diana Nguyen, Andrew Conroy, Bhamini Purandare, Eva Huang, Eric Stawiski, Alex Franzusoff, Stefanie Mandl
Journal: Cancer Research (2021)

Abstract PACT Pharma has developed an ultra-sensitive approach to validate predicted neoantigens and the cognate T cell receptors (neoTCRs) from tumor specific somatic mutations by capturing neoantigen-specific T cells from peripheral blood. This process is used in clinical trials (NCT03970382) of personalized neoTCR-T therapy for persons with solid cancers. Using the state of the art prediction pipeline and screening process, more than one hundred twenty neoantigens were predicted from 5 type of solid cancers that were validated by characterizing cognate T cells and their close to 200 unique TCRs captured from the blood of the same individual. These validated neoepitopes of 8 to 11 amino acids represent broad HLA class I coverage with &amp;gt;30 alleles to date. Our analysis revealed that mutations can occur in all positions within the epitopes. Epitope immunogenicity is potentially affected by different mechanisms including mutation position, agretopicity, as well as HLA interacting positions and/or by interactions between mutated residues and its cognate TCRs. It was observed that these validated neoepitopes comprise broad ranges of predicted HLA binding affinities, stability, and neoantigen expression levels. The analysis presented here offers insights to enable machine learning to advance rules for epitope selection and prioritization that may be important for immunological approaches to address a broad range of diseases, including cancer. Citation Format: Zheng Pan, Olivier Dalmas, Songming Peng, Kyle Jacoby, Barbara Sennino, Yan Ma, Chad Smith, Amin Momin, Allison Xu, Katharine Heeringa, Jonathan Johnston, Duo An, Boi Quach, William Lu, Diana Nguyen, Andrew Conroy, Bhamini Purandare, Eva Huang, Eric Stawiski, Alex Franzusoff, Stefanie Mandl. Tumor neoantigen profiling with validated patient-specific TCR characterization to improve neoepitope prediction [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 2177.
Adverse events in patients treated with quinolones and fluoroquinolones before and after European Medicines Agency warning
Authors: C. De Nunzio, A. Nacchia, R. Lombardo, A. Franco, G. Tema, V. Baldassarri, A. Simonato, R. Bartoletti, V. Ficarra, F. Di Giacomo, G. Disabato, A.F.M. Cicione, A. Tubaro
Journal: European Urology (2021)
Abstract 3093: Nix mediated mitophagy maintains ovarian cancer cell stemness
Authors: Tejinder Pal Khaket, Qi-En Wang
Journal: Cancer Research (2021)

Abstract Ovarian cancer is the most frequent cause of death among gynecologic malignancies. Despite the availability of effective therapeutics against cancer, the overall 5-year survival rate of ovarian cancer is still ~30-40%. Most of the lethality are due to cancer relapse and drug resistance, where cancer stem cells (CSCs) are supposed to be the key regulators. CSCs also known as tumor-initiating cells, are a small subgroup of tumor cells that can develop tumors through their capability of self-renewal and differentiation. CSCs can canonically nurture therapeutic resistance, tumor invasion, metastasis, and recurrence, which tremendously attract the scientific community for the unique CSC-based cancer therapeutics. While changing phenotypical features of CSCs complicates their identification and thereby metabolism-based alternate strategy seems to be worthy anti CSC therapy. Though autophagic degradation of mitochondria (mitophagy) based mitochondrial dynamics endowed cancer cells with stemness, but wide informational gaps and missing mechanistic knowledge further necessitates the study on mitophagy dependent CSC regulation. In this study, we investigated the potential involvement of mitophagy in maintenance of cancer cell stemness. In our experimental conditions, FACS sorted CD117/44+/+, ALDHbr and ovarian cancer stem cell like cells (CSCLCs) from OVACR4 and OVCAR3 cells showed higher mitochondrial translocation of cytosolic LC3 that directly indicates the progression of mitophagy in these subpopulations. Reduced mitocontent in CSCLCs as compare to bulk cells also supports the mitochondrial degradation. To analyze the involvement of mitophagy in stemness, mitophagy has been targeted with mDIVI a well-known mitophagy inhibitor, which downregulate the sphere forming ability and protein levels of stemness marker such as SOX2 in ovarian cancer cells. Furthermore, the mechanistic detail of mitophagy involvement in cancer stemness were evaluated. Among different mitophagy proteins, BNIP3L/NIX is highly expressed in ALDHbr and CD117/44+/+ sorted cells as compare to ALDHdim and CD117/44-/- cells, respectively. The functional implication of NIX in ovarian CSCs was verified by gene silencing approach. NIX silencing diminished the sphere forming ability and stem cell marker OCT4 that supported its crucial involvement in ovarian cancer cells stemness. In summary, our findings provide a mechanistic detail of mitophagy underlying maintenance of the CSC population in ovarian cancer and suggest that targeting of NIX based mitophagy could be exploited for the eradication of CSC and thereby tumor recurrence and drug resistance in ovarian cancer. Citation Format: Tejinder Pal Khaket, Qi-En Wang. Nix mediated mitophagy maintains ovarian cancer cell stemness [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 3093.
Low risk prostate cancer patients with negative confirmatory biopsies during active surveillance are at low risk of being treated for their disease
Authors: A. Tabcheh, J. Abi Chebel, A. Ingels, C. Champy, D. Vordos, J. Boustany, F. Gerbaud, M. Miro Padovani, A. De La Taille
Journal: European Urology (2021)
In healthy older adults, daily aspirin increased cancer mortality
Authors: Arnav Agarwal, Anne M. Holbrook
Journal: Annals of Internal Medicine (2021)

ACP Journal ClubJuly 2021In healthy older adults, daily aspirin increased cancer mortalityArnav Agarwal, MD, Anne M. Holbrook, MD, PharmD, MScArnav Agarwal, MDUniversity of Toronto, Toronto, Ontario, Canada (A.A.)Search for more papers by this author, Anne M. Holbrook, MD, PharmD, MScMcMaster University, Hamilton, Ontario, Canada (A.M.H.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202107200-074 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationMcNeil JJ, Gibbs P, Orchard SG, et al. Effect of aspirin on cancer incidence and mortality in older adults. J Natl Cancer Inst. 2021;113:258-65. https://pubmed.ncbi.nlm.nih.gov/32778876Clinical Impact RatingsGIM/FP/GP: Geriatrics: References1 Rothwell PM, Fowkes FG, Belch JF, et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011;377:31-41. [PMID: 21144578] Google Scholar2 Bibbins-Domingo K; U.S. Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016;164:836-45. [PMID: 27064677] Google Scholar3 McNeil JJ, Wolfe R, Woods RL, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med. 2018;379:1509-18. [PMID: 30221597] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Toronto, Toronto, Ontario, Canada (A.A.)McMaster University, Hamilton, Ontario, Canada (A.M.H.)Disclosures: The commentators have reported no disclosures of interest. The forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-7318.This article was published at Annals.org on 6 July 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byFSPBO-DQN: SeGAN based segmentation and Fractional Student Psychology Optimization enabled Deep Q Network for skin cancer detection in IoT applicationsCardio-Oncology: A Myriad of Relationships Between Cardiovascular Disease and Cancer July 2021Volume 174, Issue 7Page: JC74KeywordsAspirinCancer preventionCancer treatmentCardiovascular diseasesColorectal cancerDisclosureDrugsElderlyMortalityPrevention, policy, and public health ePublished: 6 July 2021 Issue Published: July 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 1634: Siglec-15 knockout inhibits tumor growth in mouse model
Authors: Peixue Li, Guofang Yan, Fuyang Wang, Xuzhen Tang, Qing Lin
Journal: Cancer Research (2021)

Abstract Several immune checkpoint blockers have been approved for treatment of certain cancers, which benefits a lot of patients with malignancies. However, the overall response rate to the current checkpoint blockers did not exceed 30% in many cases, stressing the importance of developing new immunotherapies. Siglec-15 is reported to be a critical immune suppressor functioning in parellel with PD1/PD-L1 pathway by Lieping Chen's lab in 2019. In order to verify the effect Siglec-15 in immune response against tumor growth, we generated Siglec-15 KO mice with CRISPR/Cas9 mediated genome editing and tested tumor establishment on this mice with syngeneic cell lines with or without human SIGLEC-15 overexpression. Our results showed that Siglec-15 KO inhibits tumor growth and enhances immune response in the tumor infiltrating leukocytes, supporting the role of Siglec-15 as a promising target for development of new immune checkpoint blocker. Citation Format: Peixue Li, Guofang Yan, Fuyang Wang, Xuzhen Tang, Qing Lin. Siglec-15 knockout inhibits tumor growth in mouse model [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 1634.
Abstract 564: <i>BRAF</i>V600 mutation in circulating tumor DNA can predict outcomes in early-stage melanoma
Authors: Mohamed Alaa Gouda, Jiri Polivka, Helen Huang, Inka Treskova, Kristyna Pivovarcikova, Funda Meric-Bernstam, Martin Pesta, Filip Janku
Journal: Cancer Research (2021)

Abstract Background: Up to 70% of patients with resected high-risk melanoma develop disease recurrence within 5 years. Adjuvant immunotherapy or targeted therapy can reduce the recurrence rate below approximately 60%. It is, however, at the cost of possible toxicity including long-term side effects. We hypothesize that detection of plasma-derived circulating tumor DNA (ctDNA) from patients with resected melanoma can identify patients at high-risk of disease recurrence. Methods: We developed an ultrasensitive and specific droplet digital PCR (ddPCR) - based method (Bio-Rad) to detect BRAFV600E-mutated ctDNA in pre-amplified cell-free DNA with sensitivity up to 2 mutant copies in the wild-type background. Plasma samples from patients with surgically resectable melanoma were collected before and after surgery and during follow-up visits for BRAFV600E ctDNA detection. Results obtained from ddPCR analysis were correlated with clinical outcomes. Results: Total of 53 patients with resectable melanoma (29 males [54.7%]; 15 stage III [28.3%], 22 stage II [41.5%], 10 stage I [18.9%], 3 CIS [5.7%]; 25 with mutant tissue BRAF [47.2%]) and a median age of 60 years were included in the study. BRAFV600E-mutated ctDNA was detected in 25 patients (48%) before surgery and in 17 patients (32%) after surgery. Conversion of ctDNA BRAF status (from mutant to wild-type) in preoperative and postoperative samples occurred in 11 patients (21%). Patients with detectable ctDNA in samples collected after surgery had more disease recurrences (47.1% [n=8] vs. 20.6% [n=7]; P&amp;lt;0.05) and shorter disease-free survival (26 months vs unreached median survival; P&amp;lt;0.05) - and in the cohort of patients with confirmed BRAFV600E mutation in tumor tissue shorter overall survival (35 months versus unreached median survival; P&amp;lt;0.05). At all other studied follow up timepoints, there was no significant difference in outcomes between patients with BRAFV600E-mutated ctDNA and those without. Conclusions: Our results demonstrate that ultrasensitive droplet digital PCR method can detect ctDNA in patients with resectable melanoma and that patients with detectable ctDNA in blood samples collected after surgery have inferior clinical outcomes. Citation Format: Mohamed Alaa Gouda, Jiri Polivka, Helen Huang, Inka Treskova, Kristyna Pivovarcikova, Funda Meric-Bernstam, Martin Pesta, Filip Janku. BRAFV600 mutation in circulating tumor DNA can predict outcomes in early-stage melanoma [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 564.
Abstract ND04: CLBR001+SWI019: A novel switchable CAR-T cell platform enabling functionally reversible on/off control of CAR-T cell activity for B cell malignancies
Authors: Travis Young
Journal: Cancer Research (2021)

Abstract Chimeric antigen receptor (CAR) T cell therapy targeting CD19 has been transformative in the treatment of patients with relapsed, refractory B cell malignancies. However, despite remarkable response rates, CAR-T cell therapy is limited by the potential for uncontrolled cytokine production from the genetically engineered cells, resulting in cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). Further, continuous activity of CD19-targeted CAR-T cells can result in persistent B cell aplasia due to on-target, off-tumor activity of CAR-T cells. To address these challenges, we have developed a novel “switchable” CAR-T cell therapy which affords greater versatility and the potential for improved efficacy and safety compared with existing CAR-T cell approaches. The therapy has been designed in two parts - first, a “universal” genetically engineered autologous humanized, third generation CAR-T cell (CLBR001); and second, a humanized antibody-based “switch” molecule (SWI019) with conventional drug-like properties that controls the genetically engineered cells. As designed, SWI019 controls the turning “on” and “off” of the CLBR001 CAR-T cells. We have shown, the dose of SWI019 tightly correlates with the amount of cytokine produced from CLBR001 while retaining potent in vivo activity in mouse models of leukemia. Importantly, cessation of SWI019 dosing in preclinical models led to termination of CLBR001 cytotoxic and cytokine production within 5 days. This is expected to be important in mitigating adverse events such as CRS and ICANS in patients. We further found that the cyclical nature of on/off stimulation of the switchable CAR-T cells affords greater memory and persistence of the cells in surrogate mouse models, while also allowing B cell repopulation, thus avoiding potential long-term adverse events due to B cell aplasia. A Phase 1 trial was initiated in mid-2020 for patients with relapsed, refractory B cell malignancies. We believe this approach has the potential to be applied to solid tumors in the future leveraging these “universal” CLBR001 CAR-T cells. Citation Format: Travis Young. CLBR001+SWI019: A novel switchable CAR-T cell platform enabling functionally reversible on/off control of CAR-T cell activity for B cell 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 ND04.
Nomogram of conditional survival probability of long-term Survival for Metastatic Colorectal Cancer: A Real-World Data Retrospective Cohort Study from SEER database
Authors: Lingyu Han, Weixing Dai, Shaobo Mo, Wenqiang Xiang, Qingguo Li, Ye Xu, Guoxiang Cai, Renjie Wang
Journal: International Journal of Surgery (2021)
Abstract 2488: Elucidating the role of G0S2 in breast cancer
Authors: Andrea K. Corbet, Emmanuel Bikorimana, Ratnakar Singh, Zeeshan Fazal, Raya I. Boyd, Sarah Freemantle, Michael J. Spinella
Journal: Cancer Research (2021)

Abstract Breast cancer has the second-highest cancer mortality rate for women in the United States. There are effective therapies available and a growing list of biomarkers for prognosis. However, new breast cancer targets are critically needed for patients refractory to available therapies. The present study evaluates the role of gap 0 switch 2 (G0S2), in breast cancer. Using online databases, we observed G0S2 expression is downregulated in patients with estrogen receptor-positive (ER+) breast cancer and patients with high G0S2 expression have a lower rate of relapse after treatment. Previously, our lab showed G0S2 overexpression in ER+ breast cancer cell lines resulted in decreased proliferation. Further knockout of G0S2 in murine embryonic fibroblast resulted in higher oncogenic transformation and resistance to mTOR inhibitors. These results suggest that G0S2 has a tumor suppressive function in ER+ breast cancer. To test whether G0S2 has a role in ER-negative breast cancer global knockout of G0S2 was engineered in the ER-negative MMTV-PyMT transgenic mouse model. Slower tumor progression and decreased lung metastasis was observed in G0S2-null transgenic females compared to wild-type transgenic females. These data suggest that the role of G0S2 in breast cancer in dependent on ER-status, where G0S2 functions as a tumor suppressor in ER-positive breast cancer and a tumor promoter in ER-negative breast cancer. Molecular and genetic studies manipulating G0S2 and ER in various breast cancer contexts are ongoing and will help elucidate that precise role of G0S2 in breast cancer and provide clarity on the potential of G0S2 as a novel prognostic marker and therapeutic target. Citation Format: Andrea K. Corbet, Emmanuel Bikorimana, Ratnakar Singh, Zeeshan Fazal, Raya I. Boyd, Sarah Freemantle, Michael J. Spinella. Elucidating the role of G0S2 in breast 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 2488.
処置および処置後の転帰に対するEdwards SAPIENT XTを用いた前拡張なしの直接TAVIの影響
Authors: Arai Takahide, Hayashida Kentaro, Yashima Fumiaki, Yanagisawa Ryou, Tanaka Makoto, Tsuruta Hikaru, Itabashi Yuji, Murata Mitsushige, Shimizu Hideyuki, Fukuda Keiichi
Journal: Circulation (2016)
Abstract 1101: Intercellular transfer of exosomal wild type EGFR triggers osimertinib resistance in non-small cell lung cancer
Authors: Shaocong Wu, Min Luo, Kenneth K. To, Jianye Zhang, Chaoyue Su, Hong Zhang, Sainan An, Fang Wang, Da Chen, Li-Wu Fu
Journal: Cancer Research (2021)

Abstract Epidermal growth factor receptor (EGFR)-mutated lung cancer constitutes a major subgroup of non-small cell lung cancer (NSCLC) and osimertinib is administrated as first-line treatment. However, most patients with osimertinib treatment eventually relapse within one year. The underlying mechanisms of osimertinib resistance remain largely unexplored. In this study, we found that osimertinib resistance could be triggered by the intercellular transfer of wild type EGFR protein encapsulated in exosomes from osimertinib-insensitive NSCLC cells to EGFR-mutated osimertinib-sensitive cells and then the activation of PI3K/AKT and MAPK signaling pathways both in vitro and in vivo. Importantly, osimertinib significantly increased the formation and secretion of exosomes linked to the upregulation of a Rab GTPase (RAB17). These results demonstrate the intercellular transfer of exosomal wild type EGFR maybe a novel resistant mechanism of osimertinib. These findings provide a proof of concept for targeting exosomes to prevent and reverse the osimertinib resistance. Citation Format: Shaocong Wu, Min Luo, Kenneth K. To, Jianye Zhang, Chaoyue Su, Hong Zhang, Sainan An, Fang Wang, Da Chen, Li-Wu Fu. Intercellular transfer of exosomal wild type EGFR triggers osimertinib resistance in non-small cell lung 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 1101.
Reproductive and hormonal factors and risk of incident rosacea among US White women
Authors: Wen-Hui Wu, Hao Geng, Eunyoung Cho, A. Heather Eliassen, Aaron M. Drucker, Tricia Y. Li, Abrar A. Qureshi, Wen-Qing Li
Journal: Journal of the American Academy of Dermatology (2021)
The effect of lymph node dissection on cancer-specific survival in salvage radical prostatectomy patients
Authors: M. Wenzel, C. Würnschimmel, L. Nocera, C. Collà Ruvulo, S.F. Shariat, A. Briganti, M. Graefen, L.A. Kluth, P. Mandel, F.H.K. Chun, P.I. Karakiewicz
Journal: European Urology (2021)