tbuckley/cabot-search huggingface dataset:
Abstract 4582: Mannose receptor positive macrophage infiltrate correlates with prostate cancer onset and metastatic castration-resistant disease
Authors: Jelani C. Zarif, Javier A. Baena-Del Valle, Jessica L. Hicks, Christopher M. Heaphy, Igor Vidal, Jacob Luo, Tamara L. Lotan, Jody E. Hooper, William B. Isaacs, Kenneth J. Pienta, Angelo M. De Marzo
Journal: Cancer Research (2019)

Abstract M2-Tumor Associated macrophages (M2-TAMs) can suppress inflammation within the tumor microenvironment and have been reported to modulate cancer progression. We and others have previously reported infiltration of M2 macrophages in metastatic castrate-resistant prostate cancers (mCRPC). The objective of this study was to determine whether the extent of M2 macrophage infiltration correlates with prostate cancer aggressiveness, we applied immunohistochemistry to normal prostatic tissue, localized prostate cancer and metastatic castrate-resistant prostate cancer (mCRPC) from 192 patients. To assess M2 macrophage involvement, we analytically validated an IHC assay to detect the human mannose receptor (CD206). Also, we used multiplex immunofluorescent staining to show that a small fraction of CD206 staining co-localizes with endothelial cells of lymphatic vessels, while the vast majority of staining occurs in CD68-positive macrophages. The area fraction of staining for CD206-positive macrophages increased in a stepwise fashion going from normal (i.e. non-inflammation) prostatic tissue, to primary untreated carcinomas, to hormone naive regional lymph node metastases to castration resistant prostate cancer. Complimentary studies using flow cytometry confirmed CD206-positive M2-TAM infiltration. Altogether, this study revealed a progressive increase in CD206-positive macrophages from normal prostate to metastatic CRPC. Given the immunosuppressive nature of these cells and lack of clinical success of immunotherapy for prostate cancer patients, our results provide a rationale for therapeutic development to deplete these cells in the prostate cancer microenvironment as a potential method to augment immunotherapeutic approaches in prostate cancer. Citation Format: Jelani C. Zarif, Javier A. Baena-Del Valle, Jessica L. Hicks, Christopher M. Heaphy, Igor Vidal, Jacob Luo, Tamara L. Lotan, Jody E. Hooper, William B. Isaacs, Kenneth J. Pienta, Angelo M. De Marzo. Mannose receptor positive macrophage infiltrate correlates with prostate cancer onset and metastatic castration-resistant disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4582.
Abstract 89: Reducing Overdiagnosis and Miss Rates of Kawasaki Disease at First Contact Setting
Authors: Jade Kua, Jonathan Choo, Wenyun Lin, Ann Loh, Ze Lei Tan, Teng Hong Tan
Journal: Circulation (2015)

Background: Kawasaki Disease(KD) is a challenging diagnosis at first presentation. Diagnosis relies on the 1993 American Heart Association(AHA) criteria of ≥5 days of fever with ≥4 of the following features: mucositis, cervical lymphadenopathy, non-suppurative conjunctivitis, swollen or desquamating extremities, polymorphous rash. Many present atypically and are not easily identified by the Emergency Department(ED) physician. This leads to delays in diagnosis and treatment of KD. Aim: To reduce miss rates and overdiagnosis in the ED through identifying early clinical predictors for KD, within and out of the AHA criteria. Methods: Retrospective case-controlled study on patients discharged with a diagnosis of KD at KK Women’s and Children’s Hospital (KKH) from April 2007 - December 2010. Patients admitted from the ED over the same period with initial diagnoses of KD, but with discharge diagnoses that stated otherwise formed the control group. We analysed the presentation patterns in both groups. Using multivariate logistic regression, we identified significant clinical predictors of KD. Results: The diagnostic guidelines in the ED were neither specific nor sensitive, resulting in high overdiagnosis and miss rates, respectively. Of the patients admitted with the initial diagnosis of KD, 59.2% did not have KD. 44.3% and 29.1% of KD diagnoses were missed at first visit and during reattendences respectively. Miss rates were higher in infants than in older children(≥1 year old). In older children, lymphadenopathy (OR1.79, p=0.013), non-suppurative conjunctivitis (OR2.22; p=0.001), irritability (OR2.24, p=0.005) and age (OR0.75, p&lt;0.0001) were early predictors for true KD. With reattendances, lymphadenopathy (OR2.23, p=0.002), conjunctivitis (OR3.02, p&lt;0.0001), irritability (OR1.86, p=0.040) and age (OR0.75, p&lt;0.0001) remained significant, while changes in extremities (OR1.93, p=0.008) emerges as a useful predictor. No significant predictors were found for infants. Conclusion: ED physicians should be aware of early predictors of KD. We advocate incorporating irritability into diagnostic guidelines for older children. These measures would reduce overdiagnosis and miss rates, permitting appropriate institution of early treatment.
Abstract 3353: Four vs six cycles of docetaxel and cyclophosphamide (TC) in early stage triple-negative breast cancer
Authors: Aparna Basu, Hadi A. Mohammed, Sharmeen Mahmood, Vrushali Dabak, Randa Loutfi
Journal: Cancer Research (2019)

Abstract Background: ABC trials established the use of non-anthracycline containing regimen, docetaxel and cyclophosphamide (TC) in the adjuvant setting in early stage breast cancer. In clinical practice, TC is commonly used in Stage I Triple-Negative Breast Cancer (TNBC). However, no specific recommendations exist in literature, regarding the number of cycles that can be used. i.e. TC4 vs TC6. Our aim, was to determine if TC4 is non-inferior to TC6 when used as adjuvant therapy in early stage TNBC. Methods: We retrospectively reviewed 77 patients who were diagnosed with early stage TNBC between 2007 to 2017, at our institution who had received either TC4 or TC6 as adjuvant therapy. The number of cycles the patients received were based on provider preference. The two groups (TC4, TC6) were compared in regard to stage of cancer at diagnosis based on AJCC 7thedition, grade of adverse events, recurrence and death from breast cancer recurrence. Results: Out of 77 patients, based on T stage, 25 (32.5%) were T1b, 38(49.4%) were T1c, 13(16.9%) were T2 and 1(1.3%) was T3. All patients were node negative. 53(68.8%) received TC4 and 24(31.2%) received TC6. Regarding side effects, adverse of any grade were seen in 42(79.2%) patients who received TC4 and 23(95.8%) in patients who received TC6(p=0.091). Adverse events which were grade 3 or higher were seen in 7(15.9%) in TC4 group and 3(13%) in the TC6 group (p=1.000). Recurrence in the TC4 group was seen in 4 patients (7.5%) and 3(12.5%) patient in the TC6 group (p=0.259). Death due to breast cancer recurrence was seen in 1 patient (1.9%) in the TC4 group and 1(4.1%) patient in the TC6 group. Conclusions: In this limited series, TC4 appears to be equally effective to TC6, with fewer adverse events of any grade. However, a longer follow up and a larger patient base is required to be studied for a more definitive conclusion. Citation Format: Aparna Basu, Hadi A. Mohammed, Sharmeen Mahmood, Vrushali Dabak, Randa Loutfi. Four vs six cycles of docetaxel and cyclophosphamide (TC) in early stage triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3353.
Characterization of mismatch repair deficiency in biliary tract cancer
Authors: C. Vivaldi, C. Ugolini, G. Orsi, V. Formica, S. Catanese, C. Andrea, K. Andrikou, E. Doldo, I. Pecora, D. Campani, L. Reggiani Bonetti, G. Pasquini, F. Salani, V. Massa, C. Niccoli, M. Lencioni, E. Vasile, A. Casadei Gardini, L. Fornaro, G. Fontanini, S. Cascinu, A. Falcone
Journal: Annals of Oncology (2019)
Ethical Considerations in Research on Suicide Prediction
Authors: Laura Weiss Roberts, Michele S. Berk, Kyle Lane-McKinley
Journal: JAMA Psychiatry (2019)

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Abstract 163: Identification and characterization of TGFBI in circulating tumor cell subline from pancreatic cancer cell line
Authors: Tomoki Muramatsu, Taku Sato, Minoru Tanabe, Johji Inazawa
Journal: Cancer Research (2019)

Abstract Distant metastasis to liver, lung, brain, or bone occurs via circulating tumor cells (CTCs). We hypothesized that a subset of CTCs had more malignant features than tumor cells at the primary site. We established a highly malignant cell line, Panc-1-CTC, derived from the human pancreatic cancer cell line Panc-1 (Panc-1-P) using an in vivo selection method. Panc-1-CTC cells exhibited more profound migratory and invasive abilities than Panc-1-P cells in vitro. In addition, Panc-1-CTC cells had a higher tumor-forming ability than Panc-1-P cells in vivo. To investigate whether a difference in malignant phenotypes exists between Panc-1-P and -CTC cells, we performed comprehensive gene expression array analysis. As a result, Panc-1-CTC significantly expressed transforming growth factor beta-induced (TGFBI), an extracellular matrix protein, more abundantly than did Panc-1-P cells. TGFBI is considered to regulate cell adhesion, but its functions remain unclear. In the present study, knockdown of TGFBI reduced cell migration and invasion abilities, whereas overexpression of TGFBI increased both abilities. Moreover, elevated expression of TGFBI was associated with poor prognosis in patients with pancreatic cancer. Taken together, TGFBI might be targeted for cancer therapy and its expression could be a biomarker for the prediction of prognosis in pancreatic cancer. Citation Format: Tomoki Muramatsu, Taku Sato, Minoru Tanabe, Johji Inazawa. Identification and characterization of TGFBI in circulating tumor cell subline from pancreatic cancer cell line [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 163.
Identifying Mcl-1 protein dependencies using dimerization-specific antibody biomarker for predicting response to targeted apoptosis inducing therapies.
Authors: Michael H. Cardone, Sae Rin Jean, Bahriye Karakas, Sonia Kumar, Max Narovlyansky, Bora Lim
Journal: Journal of Clinical Oncology (2019)

7038 Background: The anti-apoptotic Bcl-2 family proteins facilitate pro-survival and resistance to anti-cancer therapies. Measuring the function of these proteins has shown utility in predicting response to therapy. A method that expands the principle of BH3 profiling to solid tumors is presented. Measuring the occurrence of heterodimers of Myeloid Leukemia Cell Differentiation Protein (Mcl-1), and pro-apoptotic binding protein Bim is an indicator of cancer cell apoptotic priming state. The readout of Mcl-1 containing complex-specific biomarkers can identify survival dependencies in cancer cells potentially providing clinical utility in guiding cancer treatments. Methods: Engineered immunogens that recapitulate conformation-specific epitopes induced during binding of the Mcl-1/Bim protein complex were used to generate. monoclonal antibodies. One Heterodimer Specific Mcl-1 Bim (HsMcB) was chosen. The selective binding was confirmed using ELISA, fluorescence polarization, immunofluorescence microscopy and flow cytometry in Bim or Mcl-1 knockdown cells, and by immunohistochemistry in formalin-fixed paraffin-embedded patient tissue. Correlation of HsMcB measurements to BH3 profiling readouts from the Mcl-1 restricted Noxa peptide was explored. Results: HsMcB signal depends on both Mcl-1 and Bim protein levels. The ratio of the HsMcB to unbound protein (Mcl-1) signal ([HsMcB]/[Mcl-1]) was measured. Disruption of the complexes by BH3 mimetics targeted to Mcl-1 and depletion of Mcl-1 level using CDK9 inhibitors diminished the [HsMcB]/[Mcl-1] readout. We see correlations between these readouts and BH3 mimetic peptides readouts from the Mcl-1 specific Noxa and MS1 BH3 mimetic peptides in AML patient samples that have been treated with Mcl-1 inhibitors. Conclusions: Mcl-1 dependence is a predictive biomarker for venetoclax resistance and for response to Mcl-1 targeted therapies. Flow cytometric and IHC based measurements of a heterodimer complex offer a direct and simpler approach that harbors potential for use in clinical settings. Additional antibodies targeting Mcl-1/Bak and Mcl-1 Noxa complexes are being tested.
Efficacy and safety of daratumumab, bortezomib, and dexamethasone (D-Vd) in relapsed or refractory multiple myeloma (RRMM) based on cytogenetic risk: Updated subgroup analysis of CASTOR.
Authors: Katja Weisel, Andrew Spencer, Suzanne Lentzsch, Herve Avet-Loiseau, Tomer M. Mark, Ivan Spicka, Alberto Bosi, Vania TM Hungria, Michele Cavo, Je-Jung Lee, Ajay K. Nooka, Hang Quach, Markus Munder, Meral Beksac, Pieter Sonneveld, David Soong, Jon Ukropec, Ming Qi, Maria-Victoria Mateos
Journal: Journal of Clinical Oncology (2019)

8040 Background: MM patients (pts) with high cytogenetic risk have poor outcomes. In CASTOR, D-Vd prolonged progression-free survival (PFS) vs bortezomib and dexamethasone (Vd) alone, and exhibited tolerability in RRMM pts. We conducted a subgroup analysis of D-Vd vs Vd in CASTOR, based on cytogenetic risk. Methods: Pts received ≥1 prior line of therapy. Cytogenetic risk was based on a combined analysis of next-generation sequencing (NGS) and fluorescence in situ hybridization/karyotype testing. High-risk pts had t(4;14), t(14;16), or del17p abnormalities. Standard (std)-risk pts were confirmed negative for all 3 abnormalities. Minimal residual disease (MRD; 10 –5 ) was assessed via NGS using clonoSEQ assay V2.0. Results: In CASTOR (D-Vd, n = 251; Vd, n = 247), high-risk was confirmed in 26.7% and 25.9% of pts in the D-Vd and Vd groups, respectively. At a median follow up of 40.0 months (mo), D-Vd prolonged PFS vs Vd in pts with high- (median 13.4 vs 7.2 mo; HR, 0.40 [95% CI, 0.24-0.65]; P = 0.0002) or std-risk (median 18.4 vs 6.8 mo; HR, 0.28 [95% CI, 0.20-0.37]; P &lt; 0.0001). Higher rates of ORR, MRD negativity, and sustained MRD negativity were seen with D-Vd vs Vd (Table). D-Vd prolonged PFS in first relapse pts (high risk: median 20.1 vs 8.4 mo; HR, 0.30 [95% CI, 0.14-0.64]; P = 0.0012; std risk: median 32.6 vs 7.9 mo; HR, 0.18 [95% CI, 0.11-0.29]; P &lt; 0.0001) and PFS2 vs Vd (high risk: median 27.9 vs 18.6 mo; HR, 0.59 [95% CI, 0.37-0.94]; P = 0.0258; std risk: median 40.1 vs 21.6 mo; HR, 0.43 [95% CI, 0.32-0.59]; P &lt; 0.0001) regardless of risk. Additional data will be presented. Conclusions: Adding daratumumab to Vd demonstrates significant efficacy in high-risk RRMM. Among high-risk pts, MRD negativity was only achieved with D-Vd. These findings support use of D-Vd for high-risk RRMM. Clinical trial information: NCT02136134. [Table: see text]
Abstract 18489: Growth Hormone Releasing Hormone Agonist (GHRH-A) Restores Cardiac Function in a Rodent Model of Heart Failure With Preserved Ejection Fraction (HFpEF)
Authors: Rosemeire M Kanashiro Takeuchi, Lauro M Takeuchi, Chen C Yuan, Diana Katz, Wayne Balkan, Rhenzhi Cai, Andrew V Schally, Joshua M Hare
Journal: Circulation (2017)

Introduction: Roughly half of patients with heart failure (HF) have preserved EF (HFpEF) and this rate is increasing. The pathophysiology of HFpEF is unclear and treatment of HFpEF remains a critic...
Abstract 1191: PD-L1 expression and the tumor immune microenvironment in NUT carcinoma
Authors: Lisa M. Rooper, Nyall R. London, Janis M. Taube, William H. Westra, Justin A. Bishop, Hyunseok Kang
Journal: Cancer Research (2019)

Abstract Nuclear protein in testis (NUT) carcinoma is a rare, highly aggressive malignancy that is defined by translocations of the NUTM1 gene and has a median survival of less than one year. Although immunotherapy is an attractive novel therapeutic option, the immune microenvironment has not yet been characterized in this tumor type. We performed immunohistochemistry for PD-L1, IDO1, CD8, CD68, FOXP3 and myeloperoxidase on whole-slide sections from 9 cases of NUT carcinoma, quantified immune cell subsets using Halo image analysis software, manually scored percentage of PD-L1 and IDO1 expression in tumor cells, and classified immune cell PD-L1 expression as focal (≤5%) or non-focal (&amp;gt;5%). The 9 NUT carcinomas included 6 sinonasal, 2 mediastinal, and 1 soft tissue primaries. Median survival was 11 months (range 2-19); 7 patients (78%) died of disease while 2 (22%) had no evidence of disease at last follow up (12 and 19 months). All tumors demonstrated a dominant population of myeloperoxidase+ neutrophils, with a mean density of 954/mm2 (range 14-2311). There were also a mean 59/mm2 CD8+ cytotoxic T-cells (range 15-107), 75/mm2 FOXP3+ T-regulatory cells (range 9-349), and 54/mm2 CD68+ macrophages (range 0-417). Immune cell density did not correlate with survival. Four tumors (44%) expressed PD-L1, with mean 17% positivity (range 0-70%). PD-L1 expression was associated with improved survival (p=0.02), with higher mean PD-L1 levels in surviving patients (65% vs. 4%, p&amp;lt;0.001). Two tumors (22%) expressed non-focal PD-L1 on tumor-infiltrating lymphocytes, which was also associated with survival (100% vs. 0%, p=0.03); whereas all tumors showed non-focal PD-L1 on neutrophils and macrophages. PD-L1+ tumors also had more CD8+ T-cells per mm2 (81 vs 41, p=0.07). Three tumors (33%) expressed IDO1, which was associated with improved survival (p=0.01). Overall, NUT carcinoma demonstrates an immunosuppressive microenvironment with a dominant population of tumor-infiltrating neutrophils that also show PD-L1 expression. However, evidence of PD-L1 and IDO1 expression on tumor cells with associated cytotoxic T-cell response and improved prognosis suggests that adaptive immunity plays an important role in NUT carcinoma outcomes, raising the possibility that immunotherapy might be harnessed to augment this response. Note: This abstract was not presented at the meeting. Citation Format: Lisa M. Rooper, Nyall R. London, Janis M. Taube, William H. Westra, Justin A. Bishop, Hyunseok Kang. PD-L1 expression and the tumor immune microenvironment in NUT carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1191.
Does Addition of Estradiol Improve the Efficacy of a Rapamycin-Eluting Stent?
Authors: Tom Adriaenssens, Julinda Mehilli, Rainer Wessely, Gjin Ndrepepa, Melchior Seyfarth, Anna Wieczorek, Birgit Blaich, Raisuke Iijima, Jürgen Pache, Adnan Kastrati, Albert Schömig
Journal: Journal of the American College of Cardiology (2007)
Abstract 4598: mTORC2 suppresses GSK3-dependent, but b-TrCP-independent, Snail degradation, contributing to positive regulation of cancer cell invasion and metastasis
Authors: Shuo Zhang, Guoqing Qian, Qian-Qian Zhang, Yuying Yao, DongSheng Wang, Zhuo G. Chen, Lijing Wang, Mingwei Chen, Shi-Yong Sun
Journal: Cancer Research (2019)

Abstract Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) positively regulates cell invasion and metastasis via enhancing Snail protein translation. The connection between mTOR complex 2 (mTORC2) and cell invasion and metastasis has also been suggested. However the underlying biology or mechanism is largely unknown and thus is the focus of this study. Inhibition of mTOR with both mTOR inhibitors and knockdown of the key components including rictor, Sin1 and raptor of mTORCs decreased Snail protein levels. mTOR inhibitors promoted Snail degradation rate. Moreover, mTOR inhibitor-induced Snail reduction was rescued by proteasome inhibition. Critically, inhibition of mTORC2 (by knocking down rictor), but not mTORC1 (by knocking down raptor), enhanced Snail degradation. Therefore, it is the inhibition of the mTORC2 that induces Snail proteasomal degradation, resulting in eventual Snail reduction. Interestingly, inhibition of GSK3, but not SCF/β-TrCP, rescued Snail reduction induced by mTOR inhibitors, suggesting a GSK3-dependent, but SCF/β-TrCP-independent proteasomal degradation of Snail. Accordingly, mTOR inhibitors elevated E-Cad levels and suppressed cancer cell migration and invasion in vitro and metastasis in vivo. Collectively, the current study has revealed a novel connection between mTORC2 and positive regulation of Snail stability, thus providing a scientific base for mTORC2 in positive regulation of cell EMT, invasion and metastasis. (This study was supported by NIH/NCI R01 CA118450 and CA160522 to SYS and National Natural Science Foundation of China No. 31771578 to QQZ). Citation Format: Shuo Zhang, Guoqing Qian, Qian-Qian Zhang, Yuying Yao, DongSheng Wang, Zhuo G. Chen, Lijing Wang, Mingwei Chen, Shi-Yong Sun. mTORC2 suppresses GSK3-dependent, but b-TrCP-independent, Snail degradation, contributing to positive regulation of cancer cell invasion and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4598.
Response to: ‘Concerns about the operational definition of remission in 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus’ by Rua-Figueroa and Erausquin
Authors: Antonis Fanouriakis, George Bertsias, Dimitrios T Boumpas
Journal: Annals of the Rheumatic Diseases (2019)

We thank Drs Rua-Figueroa and Erausquin for their interest in our manuscript and their insightful comment regarding our definition of remission in Figure 1 of the 2019 update of the European League Against Rheumatism recommendations for the management of systemic lupus erythematosus (SLE).1 2 The authors claim that the definition of remission in Figure 1 (SLEDAI 0, only on hydroxychloroquine) is too stringent, as it may guide physicians towards intensification of therapy in patients with sole serological activity. Instead, …
Association of Multiple Enrichment Criteria With Ischemic and Bleeding Risks Among COMPASS-Eligible Patients
Authors: Arthur Darmon, Emmanuel Sorbets, Gregory Ducrocq, Yedid Elbez, Jeremie Abtan, Batric Popovic, E. Magnus Ohman, Joachim Röther, Peter F. Wilson, Gilles Montalescot, Uwe Zeymer, Deepak L. Bhatt, Philippe Gabriel Steg
Journal: Journal of the American College of Cardiology (2019)