tbuckley/cabot-search huggingface dataset:
Abstract 825: Genetically determined elevated C-reactive protein levels and chronic inflammation status associated with primary colorectal cancer risk: Mendelian randomization with lifestyle interactions
Authors: Su Yon Jung, Herbert Yu, Matteo Pellegrini, Jeanette C. Papp, Eric M. Sobel, Zuo-Feng Zhang
Journal: Cancer Research (2021)

Abstract Purpose: Immune-related etiologic pathways in the development of colorectal cancer (CRC) have not been convincingly determined and may be confounded by lifestyle factors or reverse causality. We investigated the genetically predicted C-reactive protein (CRP) phenotype in the potential causal pathway of primary CRC risk in postmenopausal women in a Mendelian randomization (MR) framework. Methods: We employed individual-level data of the Women's Health Initiative Database for Genotypes and Phenotypes Study, which consists of 5 genome-wide association (GWA) studies, including 10,142 women, 737 of whom developed primary CRC. We examined 61 GWA single-nucleotide polymorphisms (SNPs) associated with CRP by using weighted/penalized MR weighted-medians and MR gene-environment interactions that allow some relaxation of the strict variable requirements and attenuate the heterogeneous estimates of outlying SNPs. Results: In lifestyle-stratification analyses, genetically determined CRP exhibited its effects on the decreased CRC risk in non-viscerally obese and high-fat diet subgroups. In contrast, genetically driven CRP was associated with an increased risk for CRC in women who smoked 15 or more cigarettes/day, with significant interaction of the gene-smoking relationship. Further, a substantially increased risk of CRC induced by CRP was observed in relatively short-term users (less than 5 years) of estrogen (E)-only and also longer-term users (longer than 5 years) of E plus progestin. Conclusions: Our findings may provide novel evidence on immune-related etiologic pathways connected to CRC risk and suggest the possible use of CRP as a CRC-predictive biomarker in women with particular behaviors and CRP marker-informed interventions to reduce CRC risk. Citation Format: Su Yon Jung, Herbert Yu, Matteo Pellegrini, Jeanette C. Papp, Eric M. Sobel, Zuo-Feng Zhang. Genetically determined elevated C-reactive protein levels and chronic inflammation status associated with primary colorectal cancer risk: Mendelian randomization with lifestyle interactions [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 825.
Abstract 155: International Comparison of Pediatric In-Hospital Cardiac Arrest: Impact of Critical Care Settings for Hospital Safety and Outcome. From the Japanese Registry of CPR for In-Hospital Cardiac Arrest
Authors: Sasa Kurosawa, Naoki Shimizu, Jun Honma, Seishiro Marukawa, Naohiro Yonemoto, Hiroyuki Yokoyama, Hiroshi Nonogi, J-Rcpr Investigators
Journal: Circulation (2011)

Background: Number of paediatric intensive care unit (PICU) is scant in Japan (only 1 PICU bed available for more than 80,000 children). It may affect hospital safety issue relating to the paediatr...
Abstract 1674: WNT signal pathway activation correlates with innate resistant to immune checkpoint therapies in melanoma
Authors: Fuyu Gong, Yuezong Bai, wenzhuan Xie, Chuanliang Cui
Journal: Cancer Research (2021)

Abstract Background: Immune checkpoint inhibitors targeting the programmed cell death-1 receptor (PD-1) improve survival in a subset of patients with melanoma. There are still lots of patients could not reach the clinical benefit, even though with the positive expression of the programmed cell death 1 ligand 1 (PD-L1). Here, we aimed to research the immune resistance mechanism in melanoma. Methods: The genomic data and clinical data of the discovery cohort was obtained from The Cancer Genome Atlas (TCGA). The clinical data of validation cohort in melanoma treated by immunotherapy was retrospective collected. And tissue from patients with melanoma were performed to whole exome sequencing in a College of American Pathologists-certified and Clinical Laboratory Improvement Amendments-accredited lab. Results: Activation of WNT signaling was inferred that somatic mutations or somatic copy number alterations in WNT signaling elements including APC, WNT1, WNT4, WNT6, WNT16, CTNNB1, BCL9L, SMAD3 and SMAD4. Two cohort have been enrolled in this study, the discovery cohort from TCGA, and the validation cohort from the Chinese patients with melanoma. The frequency of WNT pathway alterations from the TCGA cohort was 28.4%, and which was represented mutually exclusive molecular subsets. In TCGA cohort, activating alteration WNT signaling were associated with shorter median OS (22.5 vs 13.6 months, p=0.047, HR=0.61 (0.37-0.89)). Conclusions: Mutations predicted to activate the WNT pathway were associated with innate resistance to immune checkpoint blockade in melanoma. Citation Format: Fuyu Gong, Yuezong Bai, wenzhuan Xie, Chuanliang Cui. WNT signal pathway activation correlates with innate resistant to immune checkpoint therapies in 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 1674.
Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19
Authors: M. Gacci, M. Coppi, E. Baldi, A. Sebastianelli, C. Zaccaro, S. Morselli, A. Pecoraro, A. Manera, R. Nicoletti, A. Liaci, C. Bisegna, S. Giancane, S. Pollini, A. Antonelli, F. Lagi, S. Marchiani, S. Dabizzi, S. Degl’Innocenti, F. Annunziato, M. Maggi, L. Vignozzi, A. Bartoloni, G.M. Rossolini, S. Serni
Journal: European Urology (2021)
Abstract 2944: Altering RAS oncogenic activity defines unique oncogenic fates
Authors: Ozgun Erdogan, Nicole L. Pershing, Christopher M. Counter
Journal: Cancer Research (2021)

Abstract RAS family oncogenes demonstrate a tropism of specific driver mutations towards different cancers and understanding the impact of individual RAS mutations on oncogenic activity, signaling, and tissue-specific cellular responses could inform on the origin of cancer as well as development of potential therapies. To genetically interrogate how each mutation could differentially alter RAS signaling output in vivo, we created a panel of mice whereby two very different oncogenic mutations, G12D and Q61R, were expressed from a Cre-inducible LSL-Kras allele encoded with native (nat) or common (com) codons to generate low or high levels of oncoprotein. We show that this panel leads to a stepwise increase in RAS activity (GTP loading) with comQ61R &amp;gt; comG12D &amp;gt; natQ61R &amp;gt; natG12D. Global activation of these alleles induced a restricted number of tumors, with increasing active Kras generally leading to a more severe disease and decreased survival. Histopathological analysis revealed that high oncogenic activity induces highly aggressive myeloproliferative disease while there is a shift to more solid tumors as the signaling is dampened. RNASeq revealed that low levels of active Kras induce transcriptional features of a plastic state while high levels have all the hallmarks of potent oncogenic activity and resultant oncogenic stress. Such findings are suggestive of potential unique vulnerabilities during tumor initiation driven by different RAS mutants that may find clinical utility in the treatment of early stage cancer to prevent recurrence. Citation Format: Ozgun Erdogan, Nicole L. Pershing, Christopher M. Counter. Altering RAS oncogenic activity defines unique oncogenic fates [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 2944.
Abstract 75: Determinants of tumor resistance to anti-angiogenic immunotherapy in mouse models of Kras-mutant NSCLC
Authors: Amaia Martinez-Usatorre, Ece Kadioglu, Chiara Cianciaruso, Alan Guichard, Bruno Torchia, Sina Nassiri, Martina Schmittnaegel, Carola H. Ries, Etienne Meylan, Ioanna Keklikoglou, Michele De Palma
Journal: Cancer Research (2021)

Abstract Immune checkpoint blockade (ICB) with PD-1 or PD-L1 antibodies has been approved for the treatment of non-small cell lung cancer (NSCLC), often in combination with chemotherapy. However, only a minority of the patients respond and sustained remissions are rare. Anti-angiogenic therapy improves tumor response to ICB in mouse models of cancer and in patients with EGFR-mutant NSCLC, but the contribution of anti-angiogenic therapy to the clinical efficacy of ICB in patients with KRAS-mutant NSCLC remains unclear. We used genetically engineered mouse models of KrasG12D/p53null NSCLC, including a mismatch repair-deficient variant (KrasG12D/p53null/Msh2null) with higher mutational burden, and longitudinal imaging of individual tumors to study tumor response and resistance to combinations of ICB, anti-angiogenic therapy, and cisplatin chemotherapy. We found that anti-angiogenic blockade of VEGFA and angiopoietin-2 (ANGPT2) with the bispecific antibody A2V was superior to single VEGFA inhibition and markedly slowed tumor progression. But, contrary to findings in other tumor models, the addition of a PD1 antibody to A2V did not provide additive benefits and even accelerated growth of a fraction of the tumors. We implicated tumor-associated macrophages (TAMs) and PD-1+regulatory T cells (T-regs) in this growth-promoting response, and identified a pre-clinical strategy involving the differential targeting of two distinct TAM subsets that unleashed the therapeutic potential of anti-angiogenic immunotherapy and achieved regression of more than 80% of the lung tumors. Citation Format: Amaia Martinez-Usatorre, Ece Kadioglu, Chiara Cianciaruso, Alan Guichard, Bruno Torchia, Sina Nassiri, Martina Schmittnaegel, Carola H. Ries, Etienne Meylan, Ioanna Keklikoglou, Michele De Palma. Determinants of tumor resistance to anti-angiogenic immunotherapy in mouse models of Kras-mutant NSCLC [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 75.
Mass infection is not an option: we must do more to protect our young
Authors: Deepti Gurdasani, John Drury, Trisha Greenhalgh, Stephen Griffin, Zubaida Haque, Zoë Hyde, Aris Katzourakis, Martin McKee, Susan Michie, Christina Pagel, Stephen Reicher, Alice Roberts, Robert West, Christian Yates, Hisham Ziauddeen
Journal: The Lancet (2021)
Abstract LB199: Trafficking of Semaphorin4D is regulated by endoplasmic reticulum chaperone GRP78
Authors: Anthony Carlos, Yuan-Li Tsai, Yan Ma, Amy Lee
Journal: Cancer Research (2021)

Abstract Localization of endoplasmic reticulum (ER) chaperones to the cell surface is an adaptive mechanism for cells to expand the functionality of these proteins in response to stress by activating signaling pathways distinct from their ER functions, thereby impacting cell survival and signaling. In cancer, cell-surface ER chaperones have been reported to regulate oncogenic signaling pathways, proliferation and cell adhesion through interactions with other cell surface proteins. The emerging role of peripheral cell surface GRP78 (csGRP78), traditionally regarded as an ER luminal chaperone, as a multifunctional co-receptor for many different types of cell surface proteins presents novel opportunities for therapeutic interventions. One such cell surface protein is Semaphorin4D (Sema4D). Sema4D was originally discovered as a cell surface cleavable ligand and neuronal axon guidance cue that mobilizes the actin cytoskeleton to facilitate neuronal growth cone homing during development. In cancer, cell surface Sema4D expression is pro-metastatic and pro-angiogenic. Sema4D has been shown to be highly expressed in the breast cancer and epidemiological studies have demonstrated that Sema4D expression in breast cancer patients confers a poor prognosis and high probability of metastatic organotropism. Our recent advances have preliminarily identified a critical role for GRP78 in facilitating Semaphorin4D (Sema4D) trafficking. We show that Sema4D forms a direct protein-protein interaction with GRP78 and that GRP78 may facilitate membrane trafficking of Sema4D to the cell surface, where it exerts pro-angiogenic and metastatic effects. Furthermore, csGRP78 may interact with and facilitate many of the functions of Sema4D. Understanding the conditions by which GRP78 contributes to surface expression of Sema4D and the downstream effects may lead to novel therapeutics that abrogate the effects of Sema4D in cancer and to the elucidation of novel mechanisms by which Sema4D trafficking in cancer is regulated by GRP78. Citation Format: Anthony Carlos, Yuan-Li Tsai, Yan Ma, Amy Lee. Trafficking of Semaphorin4D is regulated by endoplasmic reticulum chaperone GRP78 [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 LB199.
Abstract 764: Circulating tumor cell-based mRNA scoring system for prognostication of hepatocellular carcinoma - Translating HCC tissue-based mRNA profiling into a non-invasive setting
Authors: Yi-Te Lee, Na Sun, Minhyung Kim, Jasmine J. Wang, Benjamin V. Tran, Ryan Y. Zhang, Ceng Zhang, Saeed Sadeghi, Richard S. Finn, Sammy Saab, Ronald W. Busuttil, Yazhen Zhu, Hsian-Rong Tseng, Sungyong You, Ju Dong Yang, Vatche G. Agopian
Journal: Cancer Research (2021)

Abstract Background and Aims Numerous studies in hepatocellular carcinoma (HCC) have proposed tissue-based gene signatures for individualized prognostic assessments. In this study, we aim to develop the HCC circulating tumor cell (CTC) mRNA Scoring System and the HCC-CTC Risk Score (RS) panel to translate tissue-based mRNA signatures into a liquid biopsy setting for non-invasive HCC prognostication. Methods We developed the HCC CTC mRNA Scoring System by combining the NanoVelcro CTC Assay for enriching HCC CTCs and the NanoString nCounter platform for quantifying the HCC-CTC RS panel in enriched HCC CTCs. The prognostic role of HCC-CTC RS was assessed in the Cancer Genome Atlas (TCGA) HCC cohort (n=362) and validated in an independent CTC cohort (n=40). Results The HCC-CTC RS panel was developed from 8 HCC tissue-based prognostic gene signatures. Through our integrated data analysis framework, the top 10 prognostic genes highly expressed in HCC cells and lowly expressed in white blood cells were selected as the HCC-CTC RS panel. The panel accurately discriminated overall survival in TCGA HCC cohort (hazard ratio [HR]: 2.01, 95% confidence intervals [CI]: 1.39-2.91). In addition, the combined use of Scoring System and panel successfully distinguished artificial blood samples spiked with an aggressive HCC cell type, SNU-387, from those spiked with PLC/PRF/5 cells (P=0.02). Finally, the prognostic value of HCC-CTC RS was further validated in the CTC cohort (HR: 8.48, 95% CI: 1.89-38.03) by multivariable analysis. Conclusions Our pilot study demonstrates a novel interdisciplinary approach to translate tissue-based gene signatures into a liquid biopsy setting. This non-invasive approach will allow real-time disease profiling and dynamical prognostication of HCC. Citation Format: Yi-Te Lee, Na Sun, Minhyung Kim, Jasmine J. Wang, Benjamin V. Tran, Ryan Y. Zhang, Ceng Zhang, Saeed Sadeghi, Richard S. Finn, Sammy Saab, Ronald W. Busuttil, Yazhen Zhu, Hsian-Rong Tseng, Sungyong You, Ju Dong Yang, Vatche G. Agopian. Circulating tumor cell-based mRNA scoring system for prognostication of hepatocellular carcinoma - Translating HCC tissue-based mRNA profiling into a non-invasive setting [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 764.
High-dimensional and single-cell transcriptome analysis of the tumor microenvironment in angioimmunoblastic T cell lymphoma (AITL)
Authors: Joshua C. Pritchett, Zhi-Zhang Yang, Hyo Jin Kim, Jose C. Villasboas, Xinyi Tang, Shahrzad Jalali, James R. Cerhan, Andrew L. Feldman, Stephen M. Ansell
Journal: Leukemia (2021)
Abstract 1240: RRM2 and mutant p53 as therapeutic targets in TNBC
Authors: Nahid Sultana, Elizabeth A. Wilson, Howard L. Elford, Jesika S. Faridi
Journal: Cancer Research (2021)

Abstract Triple negative breast cancer (TNBC) is a highly aggressive type of cancer associated with poor prognosis and characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor type 2 (HER2). TNBC accounts for 10 - 15% of all new cases of breast cancer. TNBC is heterogenous in nature (70% basal-like) and currently doesn't have effective targeted therapy. As such, dose-dense chemotherapeutic agents used in combination, such as doxorubicin (DOXO) with cyclophosphamide, is the regimen of choice for TNBC. However, DOXO has limited efficacy as a therapeutic agent owing to acquired drug resistance and its cardiotoxic effects. Ribonucleotide reductase (RR) is the rate limiting enzyme required for the conversion of ribonucleotide to deoxyribonucleotide in DNA synthesis during cell proliferation. Didox (3,4 dihydroxybenzohydroxamic acid) is a unique RR inhibitor with iron chelating and free radical scavenging properties. We have previously identified that ribonucleotide reductase M2 (RRM2) is upregulated in TNBC cells and is a key contributor to acquired drug resistance. We found that Didox not only inhibits RRM2, but it also reduces mutant p53 protein levels and inhibits the activation of the NF-κB pathway. Through this inhibition, we found that Didox works synergistically with DOXO to inhibit TNBC tumor growth while also minimizing DOXO-induced cardiac damage in mice. In our present study, we have observed that RRM2 expression is upregulated in TNBC patients from three independent data sets and that high RRM2 levels are associated with lower recurrence free survival (RFS) and overall survival (OS). Interestingly, high levels of RRM2 were only predictive of lower RFS and OS in patients with wild-type p53 but not mutant p53. Additionally, we have found that Didox downregulates mutant p53 protein levels in TNBC cell lines but does not alter total p53 in cells with functioning p53. Our data confirms that Didox induced downregulation of mutant p53 is not a transcriptional effect. Finally, we have identified that RRM2 protein levels increase in TNBC with progression of stage as measured in patient tissue microarray analysis. Our data presents a novel and promising approach for the treatment of TNBC that involves inhibition of RRM2, NF-kB activation, and mutant p53 that merits further clinical investigation in human models. Citation Format: Nahid Sultana, Elizabeth A. Wilson, Howard L. Elford, Jesika S. Faridi. RRM2 and mutant p53 as therapeutic targets in TNBC [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 1240.
Molecular characterization of residual bladder cancer after pembrolizumab
Authors: A. Necchi, J.J. De Jong, D. Raggi, A. Briganti, L. Marandino, A. Gallina, M. Bandini, B. Dabbas, E. Davicioni, U. Capitanio, F. Montorsi, R. Seiler, J.L. Wright, Y. Lotan, P.C. Black, E.A. Gibb
Journal: European Urology (2021)
The TIS score for the prediction of long-term clinical outcomes after minimally-invasive partial and total adrenalectomy for unilateral primary aldosteronism: Results of a multicentric series
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)
Abstract 4335: Correlation Between Plaque Rupture and Morphological Features of Thin Cap Fibroatheroma in Acute Coronary Syndrome Assessed by Optical Coherence Tomography
Authors: Taishi Yonetsu, Tsunekazu Kakuta, Tetsumin Lee, Kei Takayama, Ken Kakita, Kentarou Takahashi, Ginga Yamamoto
Journal: Circulation (2009)
Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis
Authors: Chen-Hua Liu, Chi-Yi Chen, Wei-Wen Su, Chun-Jen Liu, Ching-Chu Lo, Ke-Jhang Huang, Jyh-Jou Chen, Kuo-Chih Tseng, Chi-Yang Chang, Cheng-Yuan Peng, Yu-Lueng Shih, Chia-Sheng Huang, Wei-Yu Kao, Sheng-Shun Yang, Ming-Chang Tsai, Jo-Hsuan Wu, Po-Yueh Chen, Pei-Yuan Su, Jow-Jyh Hwang, Yu-Jen Fang, Pei-Lun Lee, Chi-Wei Tseng, Fu-Jen Lee, Hsueh-Chou Lai, Tsai-Yuan Hsieh, Chun-Chao Chang, Chung-Hsin Chang, Yi-Jie Huang, Jia-Horng Kao
Journal: Clinical and Molecular Hepatology (2021)

Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited.
Considerations for a study using the Health Assessment Questionnaire to predict all‐cause mortality in early rheumatoid arthritis: comment on the article by Fatima et al
Authors: Po‐Yun Ko, Da‐Ming Yeh, James Cheng‐Chung Wei
Journal: Arthritis & Rheumatology (2021)

With great interest, we read the article by Fatima et al [1], which concluded that higher HAQ and disease activity score at 1 year were significantly associated with all-cause mortality in patients with early rheumatoid arthritis (RA). We agree with the use of discrete multivariate analysis on the cohort dataset. However, we would like to propose some methodological issues of the study.
CD11b<sup>+</sup>CTLA4<sup>+</sup> myeloid cells are a key driver of tumor evasion in colorectal cancer
Authors: Hiroshi Imazeki, Yamato Ogiwara, Mami Kawamura, Narikazu Boku, Chie Kudo-Saito
Journal: Journal for ImmunoTherapy of Cancer (2021)

Tumor metastasis is the major cause of death of colorectal cancer (CRC), and metastatic CRC remains incurable in many cases despite great advances in genetic and molecular profiling, and clinical development of numerous drugs, including immune checkpoint inhibitors. Thus, more effective treatments are urgently needed for the patients in clinical settings.We used mouse CRC metastasis models that murine Colon26 cells were subcutaneously and intravenously implanted and attempted to elucidate the tumor biological and immunological mechanisms underlying cancer metastasis. Then, we evaluated in vivo antitumor efficacy induced by agents targeting the identified molecular mechanisms using the mouse models. We validated the clinical relevancy of the findings using peripheral blood mononuclear cells obtained from stage IV metastatic CRC patients.CD11b+CTLA4+ myeloid cells were systemically expanded in the metastatic settings and facilitated tumor progression and metastasis directly via generating lipid droplets in tumor cells and indirectly via inducing immune exhaustion. These events were mediated by IL1B produced via the CTLA4 signaling from the increased myeloid cells. Blocking CTLA4 and IL1B with the specific mAbs significantly suppressed tumor progression and metastasis in the mouse models resistant to anti-PD1 therapy, and the therapeutic efficacy was optimized by blocking cyclooxygenases with aspirin.The CD11b+CTLA4+ cells are a key driver of tumor evasion, and targeting the CTLA4-IL1B axis could be a promising strategy for treating metastatic CRC. The triple combination regimen with anti-CTLA4/IL1B mAbs and aspirin may be useful in clinical settings.