tbuckley/cabot-search huggingface dataset:
Abstract 1698: Cardiovascular adverse events associated with immune checkpoint blockade: analysis of FDA-adverse events database
Authors: Jessica A. Castrillon
Journal: Cancer Research (2021)

Abstract Background: Modern therapies in oncology have increased cancer survivorship, as well as the incidence of de novo cardiovascular events. While immune checkpoint inhibitors have shown significant clinical impact in several cancer types, the frequency of immune related adverse events is common. Methods: We performed big data analytics on the FDA Adverse Events Reporting data of immunotherapy compared to chemotherapy adverse cases from January 2010- March 2020. We identified 90, 740 adverse event reports in both treatment groups. Myocarditis was significantly associated with patients receiving anti-PD-(L)1, 23.86 (95% CI 11.76-48.42, P &amp;lt; 0.001) and combination immunotherapy, 7.29 (95% CI 1.03- 51.89, P &amp;lt; 0.001). Myocarditis was most common in non-small cell lung cancer, melanoma, and renal cell carcinoma. Heart failure was significantly associated in chemotherapy compared to PD-(L)1, 0.50 (95% CI 0.37- 0.68, P &amp;lt; 0.001), CTLA4, 0.08 (95% CI 0.03-0.20, P&amp;lt;0.001), and combination immunotherapy, 0.25 (95%CI 0.13-0.48). Additionally, we observe a sexual dimorphism towards males in cardiac adverse reports for arrhythmia, 0.81 (95%CI 0.75-0.87, P &amp;lt;0.001), coronary artery disease, 0.63 (95%CI 0.53- 0.76, P &amp;lt;0.001), myocardial infarction, 0.6 (95%CI 0.53 -0.67, P&amp;lt;0.001), myocarditis, 0.59 (95%CI 0.47- 0.75, P &amp;lt; 0.001) and pericarditis, 0.5 (95% CI 0.35- 0.73, P &amp;lt;0.001). Conclusion: Our study provides the current risk estimates of cardiac adverse events in patients treated with immunotherapy. Understanding the clinical risk factors that predispose immunotherapy treated cancer patients to fulminant myocarditis is crucial in Cardio-Oncology management. Citation Format: Jessica A. Castrillon. Cardiovascular adverse events associated with immune checkpoint blockade: analysis of FDA-adverse events database [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 1698.
Abstract 941: TAM receptors as potential therapeutic targets in NF2-related schwannomas and meningiomas
Authors: Foram Dave, Sylwia Ammoun, C Oliver Hanemann
Journal: Cancer Research (2021)

Abstract Background: Mutations in the NF2 gene, which codes for the tumor suppressor Merlin, is responsible for the development of all Neurofibromatosis Type 2 (NF2)-related tumors including schwannomas and meningiomas. These tumors can also occur spontaneously in non-NF2 patients. The only available treatments for this group of tumors are surgery and radiosurgery/radiotherapy. Therefore, in a search of effective drug-based treatments for NF2-mutated schwannomas and meningiomas, we are investigating TYRO3, AXL and MERTK (TAM) receptors as new therapeutic targets. Methods: The expression and activation of TAM receptors were investigated using human Merlin-deficient meningioma and schwannoma tissues compared to control by Western blotting. Infiltration of tumor associated macrophages and their correlation to TAM family receptors were investigated using immunofluorescence double staining and flow cytometry. To understand the role of TAM receptors in the pathogenesis of schwannomas and meningiomas, in vitro shRNA knock-down and pharmacological inhibition analysis were conducted using patient-derived schwannoma and meningioma cells. Results: The results revealed overexpression and hyper-activation of AXL, MERTK, TYRO3 in human Merlin-deficient meningiomas and schwannomas. Meningiomas and schwannomas show a varied level of infiltration by M2 macrophages (CD163+) and TAM receptors are expressed on these CD163+ macrophages in addition to the tumor cells. The expression of MERTK correlates to the level of infiltrated CD163+ macrophages. MERTK forms a complex with TYRO3 in both meningioma and schwannoma tissues, and its expression is mandatory to maintain AXL and TYRO3 levels in both cell types. MERTK and AXL contribute to the increased proliferation and survival of schwannoma and meningioma primary cells in vitro. Pathological proliferation and survival of both cell types were successfully reversed by AXL inhibitor BGB324 (BerGenBio, FDA approved for AML) and MERTK inhibitor UNC2025 (preclinical) in vitro, with UNC2025 being more effective. TYRO3 did not affect the proliferation of either schwannoma or meningioma primary cells. Conclusion: Our findings suggest that TAM receptors are aberrantly expressed and activated in human Merlin-deficient meningiomas and schwannomas. Infiltration of M2 macrophages may contribute to an overall increase in the expression of TAM receptors in these tumors. AXL and MERTK are important in schwannoma and meningioma pathogenesis and are potentially good therapeutic targets. MERTK inhibitor UNC2025 has the potential to be used as a common candidate for the treatment of NF2-related tumors. Citation Format: Foram Dave, Sylwia Ammoun, C Oliver Hanemann. TAM receptors as potential therapeutic targets in NF2-related schwannomas and meningiomas [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 941.
Abstract 2441: Polysome profiling suggests VHL-dependent translational control in clear cell renal cell carcinoma
Authors: Julia A. Vassalakis, Stenio C. Zequi, Stephania M. Bezerra, Walter H. da Costa, Ola Larsson, Ivan Topisirovic, Glaucia N. Hajj
Journal: Cancer Research (2021)

Abstract ccRCC is the most common type of renal carcinoma with 80% of incidence among all types of kidney neoplasms. Most cases are localized in the kidney and potentially curable after nephrectomy however about 30% of patients will relapse with distant metastasis. Metastatic patients comprehend one third of all cases and, despite the advances in therapies, they still have low response rates. The identification of molecular mechanisms associated with ccRCC is essential to understand disease progression and treatment resistance. Genes frequently mutated in ccRCC affect the activation of signaling pathways including the mTOR pathway which can cause an unbalance in translational control. Another frequent mutation is in the tumor suppressor gene VHL which regulates response under hypoxia. Hypoxia affects gene expression by both translational and transcriptional controls that contributes to tumor formation and disease progression. Here we aim to understand how translational control can contribute to ccRCC development. We evaluated the activity of mTOR pathway and translational control in cell lines and PDX models with VHL mutation through polysome profiling. We observed lower global translational rates in both VHL mutated models suggesting an important role in translational control. Differentially translated genes identified from polysome associated RNA show a specific translational signature in response to VHL deletion. For human tumors, a cohort of 118 cases was selected between metastatic and non-metastatic patients available at A.C. Camargo Cancer Center Tumor Tissue Biobank. Polysome profiling was performed for all cases and show that increased translational rates are associated with reduced overall and progression-free survival. Citation Format: Julia A. Vassalakis, Stenio C. Zequi, Stephania M. Bezerra, Walter H. da Costa, Ola Larsson, Ivan Topisirovic, Glaucia N. Hajj. Polysome profiling suggests VHL-dependent translational control in clear cell renal cell carcinoma [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 2441.
Is diminished ovarian reserve a risk factor for miscarriage? Results of a systematic review and meta-analysis
Authors: Andrea Busnelli, Edgardo Somigliana, Federico Cirillo, Paolo Emanuele Levi-Setti
Journal: Human Reproduction Update (2021)

Anti-Müllerian hormone (AMH) serum concentration and antral follicle count (AFC), as measured by transvaginal ultrasonography, accurately reflect the antral follicle pool. However, AMH and AFC association with fertility surrogates (i.e. age at menopause, probability of conceiving naturally and ART success rate) is questioned. Miscarriage is often considered an alternative measure of reproductive capacity. Nonetheless, the impact of diminished ovarian reserve (DOR) on miscarriage incidence remains an understudied and unresolved issue.The aim of this systematic review and meta-analysis was to elucidate associations between DOR and miscarriage risk, both in women who conceived naturally and in those who achieved pregnancy through ART.Relevant studies were identified by a systematic search in PubMed, MEDLINE, Embase and Scopus, from database inception to 1 March 2021. Studies were included only if all the following conditions were met: DOR was defined using serum AMH concentration or AFC; miscarriage rate was reported separately for different groups of women categorized according to the AMH and/or AFC level; authors reported either the rate of intrauterine pregnancy loss before 22 weeks of gestation or enough data were available to calculate it.From a total of 347 publications initially identified, 16 studies were included. Pooled results from 13 retrospective studies focusing on ART pregnancies showed a significantly higher rate of miscarriage in women with a low AMH, as compared to women with a medium or high serum AMH concentration (12 042 women, random effects model, odds ratio (OR) 1.35; 95% CI, 1.10-1.66; P = 0.004; I2=50%). The only prospective study on ART pregnancies failed to show any association (61 women, risk ratio (RR) 2.95; 95% CI, 0.66-3.18; P = 0.16). Data from two prospective studies, which included naturally conceived pregnancies, showed a significantly increased miscarriage risk for women with low serum AMH. However, these data could not undergo meta-analysis owing to differing study designs. Using three retrospective studies, we observed an association between low AFC and miscarriage incidence (three retrospective studies on ART pregnancies, random effects model, OR 1.81; 95% CI, 1.02-3.21; P = 0.04; I2=64%).Our meta-analysis findings suggest that within the DOR patient subgroup, serum AMH and AFC biomarker levels may correlate with both the quantitative and qualitative aspects of ovarian reserve. However, owing to study limitations, the aetiology of this effect remains unclear and we are unable to define a causal relationship between DOR and increased miscarriage or to provide clinical recommendations based on this information. However, if confirmed by future well-designed studies, these findings would be profoundly informative for guiding women in family planning decisions.
Losartan prevents tumor-induced hearing loss and augments radiation efficacy in NF2 schwannoma rodent models
Authors: Limeng Wu, Sasa Vasilijic, Yao Sun, Jie Chen, Lukas D. Landegger, Yanling Zhang, Wenjianlong Zhou, Jun Ren, Samuel Early, Zhenzhen Yin, William W. Ho, Na Zhang, Xing Gao, Grace Y. Lee, Meenal Datta, Jessica E. Sagers, Alyssa Brown, Alona Muzikansky, Anat Stemmer-Rachamimov, Luo Zhang, Scott R. Plotkin, Rakesh K. Jain, Konstantina M. Stankovic, Lei Xu
Journal: Science Translational Medicine (2021)

Normalizing the tumor microenvironment with losartan prevents tumor-induced hearing loss and enhances radiation response in schwannoma rodent models.
Preliminary results of a randomised controlled trial to assess the benefit to apply MOSES™ technology: HoLEP vs. m-HoLEP
Authors: A. Pinero Zomeno, A. Narváez Barros, J. Placer Santos, E. Miret Alomar, J. Morote Robles, E. Trilla Herrera
Journal: European Urology (2021)
Abstract 196: Redefining cancer subtypes using multi-omics and deep learning
Authors: Altuna Akalin, Bora Uyar, Jonathan Ronen, Vedran Franke
Journal: Cancer Research (2021)

Abstract Cancer is a heterogeneous collection of diseases traditionally classified by the tissue of origin. The diversity of the molecular profiles of cancers has a big impact on the way patients are diagnosed and treated, how they respond to their prescribed treatments, the duration of survival after diagnosis, and factors such as remission, recurrence, or spread (metastasis) of the disease. While such diagnostic and prognostic outcomes are potentially predictable by taking a closer look into the changes of the genome, epigenome, transcriptome, proteome, and various other omics platforms, the contemporary cancer treatments still predominantly don't make the best use of such multi-omics profiling of patient samples. Therefore, multi-omics profiling of cancers holds great potential to define a molecularly coherent subtype definition of cancers in order to achieve the eventual goal of matching the best possible treatment to the subgroup of patients. However, the current subtypes from consortiums such as TCGA have been defined by heterogeneous methods and molecular markers by different teams. A subset of these studies have not attempted to characterize molecular subtypes, but rather taken histopathologically defined subtypes as the gold standard and tried to characterize molecular features of these subtypes. Here we evaluate TCGA cancer subtypes based on the molecular profile coherence score. This novel metric combines survival statistics, pathways information, tumor purity estimates, and mutational signatures. We expect that subtypes that are patient subgroups should display molecular signature homogeneity. We evaluate TCGA subtypes from 21 cancers using these criteria and compare the subtypes with our own definition using multi-omics data in a deep learning framework. We have refined the several subtypes from multiple cancers towards more molecularly coherent patient subgroups. Citation Format: Altuna Akalin, Bora Uyar, Jonathan Ronen, Vedran Franke. Redefining cancer subtypes using multi-omics and deep learning [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 196.
Febrile urinary tract infection as a cause for 90-day readmission after radical cystectomy for bladder cancer: Microbiology and risk factors
Authors: A. Artiles Medina, Á. Sánchez González, M. Ruiz Hernández, M. Mata Alcaraz, J.A. López Plaza, L. López-Fando Lavalle, P. Martín Dávila, M.Á. Jiménez Cidre, F.J. Burgos Revilla
Journal: European Urology (2021)
STRESS-BENESTENT同等病変にはステント術かアテローム切除術のどちらがふさわしいかの考察:ステント対方向性冠動脈アテローム切除術の無作為試験(START)結果
Authors: Tsuchikane E, Kobayashi T, Kirino M, Izumi M, Otsuji S, Tateyama H, Sakurai M, Awata N
Journal: Circulation (1999)
Hypomethylating Agent Leads to Enhanced Immunogenicity of a Dendritic Cell/Acute Myeloid Leukemia Fusion Vaccine and Prolonged Survival in an Immunocompetent Mouse Model
Authors: Myrna R. Nahas, Leandra Cole, Dina Stroopinsky, Anna Sergeeva, Athalia Rachel Pyzer, Abigail J. Washington, Malgorzata McMasters, James D. Levine, Matthew Weinstock, Shira Orr, Adam Ephraim, Jeffrey J. Molldrem, Jacalyn Rosenblatt, David E. Avigan
Journal: Blood (2017)
Low Body Mass Index in Pregnant Women with Sickle Cell Disease Is Associated with Premature Delivery in Sub- Saharan Africa
Authors: Eugenia Vicky Asare, Edeghonghon Olayemi, Yvonne Adomakoh, Enoch Mensah, Alim Swarray-Deen, Harriet Ghansah, Yvonne Osei-Bonsu, Selina Crabbe, Latif Musah, Charles Hayfron-Benjamin, Theodore Boafor, Brittany Covert, Adetola A. Kassim, Andra H. James, Mark Rodeghier, Michael R. DeBaun, Samuel A Oppong
Journal: Blood (2017)
Association of Chronic Pain With Participation in Motor Skill Activities in Children With Cerebral Palsy
Authors: Haresh D. Rochani, Christopher M. Modlesky, Li Li, Barbara Weissman, Joshua Vova, Gavin Colquitt
Journal: JAMA Network Open (2021)

Many children with cerebral palsy (CP) experience the secondary condition of pain, which is problematic because children with CP face barriers to participation in motor skill activities.1,2 Motor performance in activities of daily living among children with CP is markedly lower than that among their age-matched peers.3 Because of the potential effect of pain on children with CP, we sought to examine the association between pain and activities requiring motor skill performance (ie, difficulty dressing or bathing and participation in sport) among a nationally representative sample of US children with CP.
Abstract LB166: Evaluation of CAR-T anti-tumor response in a novel immunocompromised NOD-Prkdcem26Cd52Il2rgem26Cd22/NjuCrl mouse model
Authors: Rashmi Bankoti, Amit Joshi, Lasse Jorgensen, Andreas Kongsgaard, Maddalena Adorno, Benedetta Nicolis di Robilant
Journal: Cancer Research (2021)

Abstract Background: The development of immunocompromised mice revolutionized the field of cancer and stem cell research. Due to the lack of mature B and T lymphocytes, SCID (severe combined immunodeficiency disease) mice are ideal for xenoengraftment of human cells and tissue, including patient-derived tumor cells, hematopoietic stem cells and T cells. Over the years, the SCID models have been implemented to increase the efficiency of engraftment and NSG (NOD-SCID;IL2Rgammanull) has become the most reliable in vivo human cancer model. Here we compared NSG with the novel mouse strain NCG for immune-oncology applications, in particular for CAR-T therapy. NCG (NOD-Prkdcem26Cd52Il2rgem26Cd22/NjuCrl) is a recently developed triple immunodeficient mouse strain, created by sequential CRISPR/Cas9 editing of the PRKDC and IL2rg loci in the NOD/Nju strain. For this purpose, we engrafted NALM-6 and CHLA-55 tumor cell lines and treated them with CD19 and GD2.CAR T cells, respectively. Results: Four different operators generally considered NCG mice to be easier to handle. NCG mice were a bit smaller and have a much smaller spleen compared to age-matched NSG mice. Tumor engraftment was particularly rapid in NCG while the dissemination to organs was comparable. Generally, NCG showed signs of sickness earlier and upon lower tumor burden. When treated with CAR-T cells, in vivo anti-tumor response was comparable, both in a leukemia mouse model (96.6% NSG vs 97.7% NCG) and in a disseminated neuroblastoma model (67.3% NSG vs 57.8% NCG).Conclusion: Our preliminary data show that NCG mice are a suitable immunocompromised host for CAR-T pre-clinical studies. Citation Format: Rashmi Bankoti, Amit Joshi, Lasse Jorgensen, Andreas Kongsgaard, Maddalena Adorno, Benedetta Nicolis di Robilant. Evaluation of CAR-T anti-tumor response in a novel immunocompromised NOD-Prkdcem26Cd52Il2rgem26Cd22/NjuCrl 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 LB166.
Texas promises $10 000 for people who enforce the state’s new limit on abortions
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

Abortion and civil rights campaigners in the US are challenging a law set to take effect in Texas on 1 September that bans abortions after six weeks and rewards anyone who helps to prosecute sucessfully anyone helping a woman to break the law with a reward of $10 000 (£7200; €8560).1

Someone could be sued if they advised a woman seeking an abortion, drove her to a clinic, lent her money for the abortion, or helped provide an abortion, such as a doctor or nurse.

The new law2—known as SB 8 or the “Texas Heartbeat Act” and which would bring down the limit for abortion from the current 20 weeks—is unconstitutional and would lead to lawsuits, …
Abstract 1238: Treating estrogen receptor (ER)-negative and triple-negative breast cancer by targeting STAT3 signaling with putative STAT3 inhibitors
Authors: Hyejin Kim, Doerte R. Fricke, Jimin Xu, Haiying Chen, Jia Zhou, Qiang Shen
Journal: Cancer Research (2021)

Abstract Approximately 20% to a quarter of breast cancer cases are estrogen receptor (ER)-negative breast cancer (ENBC), including the most aggressive subtype, triple-negative breast cancer (TNBC), which spreads early and shows poor prognosis. ENBCs do not respond to selective ER modulators such as tamoxifen. Therefore, there is an urgent need for non-ER-based therapies for ENBC. Recently, STAT3 was found to play an important role in maintaining cancer stem cells in vitro and in mouse models of human cancers. In addition, during mammary carcinogenesis, STAT3 is highly activated in mammary epithelial cells involving in mammary epithelial cell transformation, tumor initiation, progression, and metastasis. STAT3 has been traditionally considered as non-targetable or undruggable, and there is currently a lack of FDA-approved STAT3 inhibitors for clinical use. We recently developed a putative STAT3 inhibitor, HJC0152, and a series of HJC0152-based analogues as orally bioavailable STAT3 inhibitors. These small molecules have been evaluated and a number of them showed low micro-molar potency in inhibiting the proliferation of a panel of breast cancer cell lines. Compound JMX0804 showed improved anti-proliferative effects against the highly aggressive TNBC cell line MDA-MB-231 and other ER+ and ER- breast cancer cell lines in comparison to HJC0152. JMX0804 inhibited STAT3 phosphorylation at the Tyr705 residue and induced apoptosis in MDA-MB-231 cells. In vivo, mice treated with JMX0804 at a 10 mg/kg dose via i.p. showed reduced growth of xenograft tumors arisen from MDA-MB-231 cells, with minimal impact on general health and body weight. Our current research supports the notion that JMX0804 suppresses breast cancer growth by inhibiting breast cancer cell proliferation and inducing apoptosis via mediating STAT3 signaling. JMX0804 is currently undergoing further characterization for breast cancer metastasis and mechanisms of action as well as optimization to improve drug properties including potency and safety profile. This work is supported by NIH/NCI grant R01 CA231150. Citation Format: Hyejin Kim, Doerte R. Fricke, Jimin Xu, Haiying Chen, Jia Zhou, Qiang Shen. Treating estrogen receptor (ER)-negative and triple-negative breast cancer by targeting STAT3 signaling with putative STAT3 inhibitors [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 1238.
Secretory Otitis Media: The Cantekin Affair
Authors: Arnold S. Relman
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Dr Rennie's commentary on "The Cantekin Affair"<sup>1</sup>raises interesting questions but, in my judgment, comes to dubious conclusions. Should the<i>New England Journal of Medicine</i>(<i>NEJM</i>) have reviewed the first version of the manuscript by Cantekin et al?<sup>2</sup>Rennie says yes, but in response to an inquiry I made immediately after receiving the Cantekin manuscript in 1987, officials at the University of Pittsburgh told me that Cantekin was under investigation for unprofessional conduct. Under the circumstances I had no choice but to decline any further consideration of Cantekin's manuscript. The decision by<i>JAMA</i>in 1988 to reject the same manuscript seems to have been based on similar considerations, so I don't see how Rennie can fault the<i>NEJM</i>without faulting his own journal as well. Was it wise for<i>JAMA</i>to have decided to publish a revised version of the Cantekin manuscript more than 3