tbuckley/cabot-search huggingface dataset:
Abstract A78: Pre-existing, poly-resistant cancer stem cells in high-grade serous ovarian cancer
Authors: Jingzhong Xie, Yusuke Yamamoto, Audrey-Ann Liew, Bailiang Wang, Rajasekaran Mahalingam, Marcin Duleba, Wei Rao, Suchan Niroula, Kristina Goller, Yanting Zhang, Shan Wang, Amir Jazaeri, Peter Davies, Suzy Torti, Giulio Draetta, Matthew Anderson, Molly Brewer, Christopher Crum, Frank McKeon, Wa Xian
Journal: Clinical Cancer Research (2020)

Abstract High-grade serous ovarian carcinoma (HGSOC) is the most common and lethal form of epithelial ovarian cancer. While HGSOCs respond well to platinum and taxane chemotherapy, the majority of patients eventually relapse with treatment-resistant tumors. This new and ominous resistance property of recurrent tumors is generally thought to be acquired in a process aided by the mutagenic activities of the chemotherapy itself. However, using advanced and robust technology that enables the direct cloning of cancer stem cells (CSCs) from HGSOCs, our study challenges the notion that chemotherapy resistance is acquired. In particular, patient-specific “libraries” of CSCs generated from therapy-naive tumors show that, while the majority of the CSCs are rapidly killed by platinum-taxane treatment, a discrete subset is highly resistant to these drugs to which they had no prior exposure. More telling is that these pre-existing, platinum-taxane resistant CSCs also display a profound “polyresistance” to a wide range of unrelated chemotherapeutic drugs. Importantly, gene expression profiles of polyresistant CSCs are highly uniform within a particular patient and clearly distinct from those of sensitive clones. This finding suggests that resistant clones within a patient carry the same gene signature, suggesting that resistance is a singular and knowable event in each patient. Comparing the resistance gene expression signatures across patients is revealing a very limited set of common pathways involving nuclear receptors that likely hold the key to the polyresistance phenomena. Taken together, our study supports the concept that these poly-resistant variants exist and can be cloned from most if not all HGOC patients. Further, the cloning of these polyresistant cells sets in motion the possibility that such variants can be exploited to identify both key pathways of polyresistance and drugs that specifically and pre-emptively eliminate these clones to prevent onset of recurrent disease. Citation Format: Jingzhong Xie, Yusuke Yamamoto, Audrey-Ann Liew, Bailiang Wang, Rajasekaran Mahalingam, Marcin Duleba, Wei Rao, Suchan Niroula, Kristina Goller, Yanting Zhang, Shan Wang, Amir Jazaeri, Peter Davies, Suzy Torti, Giulio Draetta, Matthew Anderson, Molly Brewer, Christopher Crum, Frank McKeon, Wa Xian. Pre-existing, poly-resistant cancer stem cells in high-grade serous ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A78.
Abstract 1048: Genomic analysis of patients with relapsed ovarian cancer enrolled in a phase II trial of nivolumab and bevacizumab
Authors: Elizabeth H. Stover, Svitlana Tyekucheva, Yiwen Liu, Jennifer D. Curtis, Richard T. Penson, Joyce F. Liu
Journal: Cancer Research (2020)

Abstract We analyzed genomic alterations in patients with relapsed ovarian cancer treated with combined nivolumab and bevacizumab in a phase II clinical trial, in order to identify potential biomarkers of response. Thirty-eight patients were treated with nivolumab and bevacizumab and the previously reported overall response rate was 28.9% (Liu et al, JAMA Oncology, 2019). Formalin-fixed paraffin-embedded patient tumor samples (acquired pre-treatment) underwent whole-exome sequencing, followed by quality control filtering and analysis of mutations, insertions/deletions, copy-number alterations, and mutational signatures using established methods. Differences in genomic event rates were assessed between response groups, as defined by presence or absence of objective response or clinical benefit. We describe the genomic alterations in all patients treated with nivolumab and bevacizumab, including several long-term responders with treatment duration &amp;gt;24 months. The observed alterations in the patient cohort reflected known patterns of common mutations (e.g. TP53) and copy-number alterations (e.g. MYC amplification) in ovarian cancer. Within the limits of sample size, no significant differences in frequency of specific mutations were observed between response groups, with the possible exception of mutations in SETD1B, a histone methyltransferase, which were more frequent in the subset of patients lacking clinical benefit. BRCA1/2 mutation rate was similar between groups. Tumor mutational burden was not significantly different between groups. Initial exploratory analysis for copy-number alterations did not reveal genes with differential copy-number alterations between the response groups, and further analyses of copy-number alterations and mutational signatures are in progress. In summary, we describe genomic biomarker analysis from tumors of patients with relapsed ovarian cancer receiving treatment with nivolumab and bevacizumab. Taken together, we did not identify genomic alterations that clearly distinguish responding and non-responding patients in the data evaluated to date. Analysis of targeted RNA-sequencing data is planned as a next step. Further studies are needed to identify genomic or transcriptomic biomarkers of responses to checkpoint blockade and anti-angiogenic therapy in ovarian cancer. Citation Format: Elizabeth H. Stover, Svitlana Tyekucheva, Yiwen Liu, Jennifer D. Curtis, Richard T. Penson, Joyce F. Liu. Genomic analysis of patients with relapsed ovarian cancer enrolled in a phase II trial of nivolumab and bevacizumab [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1048.
Residual Challenges in Radial Approach for Percutaneous Coronary Interventions
Authors: Pierfrancesco Agostoni, Carlo Zivelonghi, Paul Vermeersch
Journal: JAMA Cardiology (2020)

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Abstract 2763: Identification of mouse embryo genes in human cancer using cBioportal
Authors: Miranda Xiong, Christina Wang, Eric Chen, Arthur Hu, Raymond Luo
Journal: Cancer Research (2020)

Abstract Cancer is the second leading cause of death, often without a cure. There are many genetic factors that can either cause cancer, worsen existing conditions, or shorten a person's life span; however, it is not fully understood. During embryogenesis, many genes are expressed during a short window of the developmental stages and then switched off in adults. It is known that some of the embryogenesis specific genes are switched on in tumors. The purpose of this study was to identify genes that are exclusively expressed in the central nervous system (CNS) of the E14.5 mouse embryo (Dlez-Roux, G. et al) associated with cancer to provide a foundation for future research.Using cBioPortal, we queried the TCGA PanCancer Atlas Studies (32 studies and 10,967 samples) by each of the 80 genes expressed in the CNS of E14.5 mouse embryo. The data types analyzed included cancer type percentages and survival estimate (overall and disease/progression-free Kaplan-Meier estimate). To identify genes that are relevant in human cancer, the 80 genes were filtered based on three criteria: whether the gene mutations were found in at least 10% of various cancer types, whether the p-value for either the overall survival Kaplan-Meier Estimate, and of the disease/progression-free Kaplan-Meier Estimate was equal or less than 0.05. Fourteen genes carried mutations in more than 10% of various cancer types. Mutations in nine genes significantly decreased cancer patients' overall survival, but mutations in one gene significantly improved overall survival. Mutations in ten genes also significantly decreased the patients' disease/progression-free survival. Three genes demonstrated a high mutation rate (&amp;gt;15%) and significantly reduced patients' survival in both overall survival and disease/progression-free estimates. None of these genes have been identified as cancer driver genes. We report here that many of the CNS E14.5 mouse embryonic genes are mutated in human cancers and some of the mutations may predict cancer patient outcome. Using the same approach, we will evaluate whether these genes are correlated with the manifestation of all cancers or a subset of cancer types. In the future, we would like to obtain the opportunity to study the role of these genes in cancer development or cancer treatment in a laboratory. Dlez-Roux, G. et al: A high-resolution anatomical atlas of the transcriptome in the mouse embryo. PLoS Biol. 2011This study was supervised by Dr. Yangjun Qin, and all authors contributed equally. Citation Format: Miranda Xiong, Christina Wang, Eric Chen, Arthur Hu, Raymond Luo. Identification of mouse embryo genes in human cancer using cBioportal [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2763.
Abstract 3331: Role of innate immune cells in the development of vessel co-opting CRC liver metastases
Authors: Thomas Z. Mayer, Diane H. Kim, Miran Rada, Stephanie Petrillo, Anthoula Lazaris, Peter Metrakos
Journal: Cancer Research (2020)

Abstract Approximatively 50 % of patients who undergo resection for primary colorectal cancer will develop liver metastases. Liver metastases present as two major histopathological growth patterns (HGP) the desmoplastic and the replacement HGP. In the desmoplastic HGP, the cancer cells are surrounded by a desmoplastic stromal ring preventing their contact with the normal liver. In the replacement HGP, the cancer cells infiltrate the normal liver and replace hepatocytes near the tumour periphery. We have found that the desmoplastic HGP tumors derive their blood supply through angiogenesis while the replacement HGP tumors are non-angiogenic and co-opt the blood vessel of the liver they invade. Furthermore, we have published that patients under chemotherapy presenting with a vessel co-opting phenotype have a worse pathological response and five-year overall survival compared to patients presenting with angiogenic liver metastases. Their prognosis is worse when treated with bevacizumab an anti-VEGF antibody used alongside chemotherapy. CRCLM are considered immunologically cold lesions, with low numbers of infiltrating T-cells, and thought to be unlikely to benefit from immunotherapies. We have recently found that neutrophils and macrophages but not lymphocytes infiltrate vessel co-opting lesions to a greater extent than angiogenic lesions. Using flow cytometry and the Nanostring GeoMx spatial protein profiling platform capable of detecting up to 96 proteins simultaneously on FFPE tissue slices, we established the immunoprofile of immune cells recruited to angiogenic or vessel co-opting CRCLM lesions in chemonaive and treated patients. Many studies have demonstrated that neutrophils and macrophages play an important role in tumor progression, modification of the ECM, angiogenesis, and immunosuppression. We hypothesize that innate immune cells can facilitate blood vessel co-option of CRCLM lesions and contribute to an immunosupressive environment favorable to tumor growth. Fully understanding the role of the innate immune system in the developmend of vessel co-opting CRCLM tumors could allow for the development of immunotherapies capable of converting vessel co-opting lesions into angiogenic lesions that are more successfully treated with chemotherapy and anti-angiogenic therapies. Citation Format: Thomas Z. Mayer, Diane H. Kim, Miran Rada, Stephanie Petrillo, Anthoula Lazaris, Peter Metrakos. Role of innate immune cells in the development of vessel co-opting CRC liver metastases [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3331.
Gender Disparity in Awards in General Surgery Residency Programs
Authors: Lindsay E. Kuo, Heather G. Lyu, Molly P. Jarman, Nelya Melnitchouk, Gerard M. Doherty, Douglas S. Smink, Nancy L. Cho
Journal: JAMA Surgery (2020)

<h3>Importance</h3> Women are disproportionately underrecognized as award winners within medical societies. The presence of this disparity has not been investigated in training programs. <h3>Objective</h3> To determine the presence of a gender disparity in award winners in general surgery residency programs. <h3>Design, Setting, and Participants</h3> In this retrospective survey study, 32 geographically diverse academic and independent general surgery residency programs were solicited for participation. The 24 participating programs (75.0%) submitted deidentified data regarding the gender distribution of residents and trainee award recipients for the period from July 1, 1996, to June 30, 2017. Data were analyzed from September 11, 2017, to December 21, 2018. <h3>Exposures</h3> Time and the proportion of female trainees. <h3>Main Outcomes and Measures</h3> The primary outcome was the percentage of female award winners. A multilevel logistic regression model accounting for the percentage of female residents in each program compared the odds of a female resident winning an award relative to a male resident. This analysis was repeated for the first and second decades of the study. Award winners were further analyzed by type of award (clinical excellence, nonclinical excellence, teaching, or research) and selection group (medical students, residents, or faculty members). <h3>Results</h3> A total of 5030 of 13 760 resident person-years (36.6%) and 455 of 1447 award winners (31.4%) were female. Overall, female residents were significantly less likely to receive an award compared with male residents (odds ratio [OR], 0.44; 95% CI, 0.37-0.54;<i>P</i> &lt; .001). During the first decade of the study, female residents were 70.8% less likely to receive an award compared with male residents (OR, 0.29; 95% CI, 0.19-0.45;<i>P</i> &lt; .001); this improved to 49.9% less likely in the second decade (OR, 0.50; 95% CI, 0.42-0.61;<i>P</i> &lt; .001). Female residents were less likely to receive an award for teaching (OR, 0.33; 95% CI, 0.26-0.42;<i>P</i> &lt; .001), clinical excellence (OR, 0.44; 95% CI, 0.31-0.61;<i>P</i> &lt; .001), or nonclinical excellence (OR, 0.69; 95% CI, 0.48-0.98;<i>P</i> = .04). No statistical difference was observed for research award winners (OR, 0.76; 95% CI, 0.42-1.12;<i>P</i> = .17). The largest discrepancies were observed when award recipients were chosen by residents (OR, 0.23; 95% CI, 0.14-0.39;<i>P</i> &lt; .001) and students (OR, 0.32; 95% CI, 0.25-0.42;<i>P</i> &lt; .001) compared with faculty members (OR, 0.52; 95% CI, 0.42-0.66;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> This study found that female residents were significantly underrepresented as award recipients. These findings suggest the presence of ongoing implicit bias in surgery departments and training programs.
Shared and restricted T-cell receptor usage is crucial for carbamazepine-induced Stevens–Johnson syndrome. Journal of Allergy and Clinical Immunology
Authors: T. M. Ko, W. H. Chung, C. Y. Wei, H. Y. Shih, J. K. Chen, C. H. Lin, Y. T. Chen, S. I. Hung
Journal: Journal of Allergy and Clinical Immunology (2011)
FRI0196 Relationship between bronchoalveolar lavage (bal) and high resolution-ct (hrct) findings in scleroderma lung disease
Authors: R La Corte, D Santilli, R Tieghi, A Lo Monaco, F Ravenna, R Galeotti, N Prandini, F Trotta
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> We assessed the presence of alveolitis by means of BAL and its correlations with HRCT findings in the diagnosis of systemic sclerosis (SSc)-related interstitial lung disease (SSc-ILD). <h3>Methods</h3> 43 nonsmoking patients (pts) with SSc, with a mean age of 54.62 ± 2.08 years (range 23–74), underwent to: bronchoscopy with BAL according to the 1990 American Thoracic Society guidelines;<sup>1</sup> lung HRCT, graded according to a scoring system proposed by Warrick <i>et al</i>.;<sup>2</sup> and SSc-related antibodies testing. <h3>Results</h3> Patients with alveolitis (A) and those without alveolitis (NA), divided according to BAL results, were comparable as to mean age and duration of disease, to the prevalence of diffuse or limited subset of disease, to mean values of skin score and to the results of examinations with respiratory function tests, diffusing capacity for carbon monoxide, and inhaled 99mTc-DTPA for the measure of alveolar clearance rate performed as part of the whole clinical assessment. BAL showed the presence of alveolitis in 18/43 pts (41.8%) with cell profiles so distributed: lymphocytic (L) in 5/18 pts (27.7%); eosinophilic (E) in 1/18 (5.5%); pure neutrophilic (N) in 5/18 (27.7%) and a mixed pattern (3 N+L, 3 N+E, 1 N+L+E) in 7/18 (38.8%). Both "total HRCT" score (14.3 ± 1.2 vs 9.2 ± 1.2; p = 0.01) and "severity of disease" score (8.8 ± 0.8 vs 6.0 ± 0.8; p = 0.02) yelded significantly higher values in A pts compared with NA pts. Among HRCT abnormalities, only "honeycombing" (HC) was significantly more frequent in A pts (p = 0.033); while the presence of "ground glass" (GG), "irregular pleural margins", "septal/subpleural lines" and "subpleural cysts" showed no differences between A and NA pts. Anti Scl-70 positivity was more prevalent in A pts (p = 0.015) and, whether or not alveolitis was present, it correlated with higher "total HRCT" scores (p = 0.039). <h3>Conclusion</h3> Seemingly, GG cannot be unambiguously considered as the radiographic sign of alveolitis, since the latter is more prevalent in patients with HC which so, far from being the equivalent of a purely fibrotic outcome, could represent pathologic lung tissue that still retains some ongoing and potentially treatable inflammatory activity. Moreover, we confirm the role of anti Scl-70 as a negative prognostic marker associated with SSc-ILD. <h3>References</h3> Am Rev Respir Dis. 1990;142:481 J Rheumatol. 1991;18:1520
Abstract 1690: Blockade of antitumor milieu-induced tumor cell PIM2 expression potently synergizes with anti-PD-L1 therapy in hepatocellular carcinoma
Authors: Juncheng Wang, Shi-Xun Lu, Jinbin Chen, Dongping Chen, Minshan Chen, Zhongguo Zhou
Journal: Cancer Research (2020)

Abstract Background &amp; Aims: Despite being a typical oncogene, PIM kinase has been reported to suggest a favorable prognosis in some solid tumors, but no research has yet explored the underlying mechanisms. Furthermore, an inconsistent prognosis also hinders the clinical application of PIM inhibitors. We aimed to explore the clinical significance and regulatory mechanism of PIM2, as well as the potential clinical application of PIM2 inhibitor in hepatocellular carcinoma (HCC). Methods: PIM2 expression was assessed in 464 HCC patients who underwent curative resection, and its correlations with prognosis, immune status, and tumor infiltrating leukocytes (TILs) were investigated. Moreover, the underlying regulatory mechanisms of PIM2 and the clinical application of PIM2 inhibitor were also studied. Results: We found that PIM2 primarily displayed an oncogenic function in HCC. However, elevated PIM2 expression in tumor cells predicted a favorable prognosis. Mechanistically, high PIM2 expression in tumors was associated with an adaptive immune response elicited by TILs, and IL-1β, together with TNF-α and IFN-γ, derived from TILs induced the expression of PIM2 by activating the p38/Erk/MAPK and NF-κB signaling pathways in tumor cells. Specifically, high PIM2 expression in tumors was significantly correlated with a high density of T cells and monocytes, and activated T cell-secreting IFN-γ-polarized monocytes induced the tumor cell PIM2 expression in the tumor milieu. Moreover, blockade of antitumor milieu-induced tumor cell PIM2 expression potently augmented the therapeutic efficacy of anti-PD-L1 therapy in HCC. Conclusions: Our study provides important insights into a possible adaptive immune resistance mechanism by which the antitumor milieu induces oncogenic PIM2 expression in tumor cells. Moreover, specific inhibition of PIM2 in tumor cells augments the therapeutic efficacy of anti-PD-L1 therapy in HCC. Citation Format: Juncheng Wang, Shi-Xun Lu, Jinbin Chen, Dongping Chen, Minshan Chen, Zhongguo Zhou. Blockade of antitumor milieu-induced tumor cell PIM2 expression potently synergizes with anti-PD-L1 therapy in hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1690.
A Food and Drug Administration analysis of survival outcomes comparing the Adjuvant Paclitaxel and Trastuzumab trial with an external control from historical clinical trials
Authors: L. Amiri-Kordestani, D. Xie, S.M. Tolaney, E. Bloomquist, S. Tang, A. Ibrahim, K.B. Goldberg, M.R. Theoret, R. Pazdur, R. Sridhara, E.P. Winer, J.A. Beaver
Journal: Annals of Oncology (2020)