tbuckley/cabot-search huggingface dataset:
Abstract P6-16-08: Evaluation of cytochrome P450 4A11 overexpression in breast cancer cells in vitro and in vivo
Authors: Sehar Ali, Thaiz Borin, Ali Arbab
Journal: Cancer Research (2020)

Abstract Metastatic breast cancer (BC) is a highly invasive form of cancer that contributes greatly to patient mortality. Due to the complex mechanisms underlying cancer growth and metastasis, novel therapeutic targets must be found to increase patient survival. One such target is the cytochrome P450 4 (CYP4) metabolic pathway leading to the production of 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE is a lipid signaling molecule that promotes both tumor cell proliferation and neovascularization in tumors by inducing the proliferation and migration of endothelial cells, therefore promoting BC tumor survival. N-hydroxy-N’-(4-butyl-2 methyl phenyl) formamidine (HET0016) is a selective inhibitor of 20-HETE synthesis, thus impairing tumor growth and neovascularization. This study aims to investigate changes in BC (MDAMB231 and MCF7) cell lines overexpressing CYP4A11, a human CYP4 enzyme, with and without HET0016 treatment. To accomplish this, cells that overexpressed CYP4A11 were produced using lentivirus infection and confirmed via western blot. Tumor cell aggressiveness was assessed in vitro using migration and proliferation assays. Tumor growth with and without CYP4A11 overexpression was also measured in vivo using athymic nude mice. The results demonstrated that cells overexpressing CYP4A11 showed protein levels 4 times higher than the non-modified cells. MDAMB231 is a triple-negative BC (TNBC) that, when overexpressing CYP4A11, demonstrated increased proliferation capacity and significant increased tumor growth compared to non-modified cells. TNBC cells overexpressing CYP4A11 also showed increased motility. However, modified MCF7 cells did not show significant alterations when compared to non-modified MCF7 cells. Additionally, all cells treated with HET0016 showed decreased migration in the first 24 hours. In conclusion, these results demonstrate that the overexpression of CYP4A11 in TNBC cells increased tumor aggressiveness, proving this pathway to be an important target for therapeutic inhibition. Citation Format: Sehar Ali, Thaiz Borin, Ali Arbab. Evaluation of cytochrome P450 4A11 overexpression in breast cancer cells in vitro and in vivo [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-16-08.
How can I keep calm during self-isolation?
Authors: Abi Rimmer
Journal: BMJ (2020)

How can I keep calm during self-isolation?On top of the stress of work, there are now additional pressures to deal with at home, especially if you are self-isolating.Abi Rimmer asks experts how best to manage these Abi RimmerThe BMJ Kids can learn through playAdam Dobson, head of early years foundation stage at Thames View Infants School, Barking, says, "As an early years teacher, and a parent of a five year old, I've experienced the difficulty in trying to recreate the classroom at home.
Abstract P3-08-72: Poor prognosis in elderly patients with breast cancer resulted from under-treatment in patients with triple negative breast cancer and mortality from other than breast cancer
Authors: Gilseong Moon, Ji wool Ko, Hany Noh, In-Jeong Cho, Jong-in Lee, Airi Han
Journal: Cancer Research (2020)

Abstract Background: Breast cancer is the leading cause of malignant disease in Korean women nest to thyroid cancer. Age is one of the significant risk factor and Korean population is aging rapidly, almost 1.5 times older than a half century ago, from 52.4 years in 1960 to 78.5years at 2005. While it is uncertain the proportional incidence is also increasing, absolute number of elderly patients is increasing and unmet clinical needs and unanswered questions are remained in the clinical practice for elderly patients. The aim of this study is to outline breast cancer in elderly patients and examine survivals by clinicopathologic factors such as age, stage and disease subtype. Material and Methods: Patients who were diagnosed and completed their primary treatment for breast cancer from 2000 to 2013 were included. Clinicopathologic data was collected with retrospective data review and survival data and risk factors, if the survival was statistically significant, were obtained. Results: 1103 patients with invasive breast cancer were included. Mean age was 52.71±11.478(22-89). Subjects were divided into three group, &amp;lt;40 (n=147, 35.9±3.704), 40-60 (n=680,49±5.131), &amp;gt;60(n=276,68.6±5.62). Patients over 60 had statistically worse overall survival(p=0.011) and distant disease free survival(p=0.012) with Kaplan-Meier method with log rank test and hazard ratio(HR) of elderly was 2.206 with 1.046-4.658 96% Confidence Interval(CI). For the worse prognosis of elderly, triple negative breast cancer who got less than standard systemic treatment (HR=4.836, 95% CI, 1.514-15.452) and mortality from other than breast(HR=2.395, 95% CI,1.106-5.188) cancer were significantly correlated with higher mortality in elderly patients. Conclusion: Elderly patients with breast cancer experience significant worse survival when they got less than standard systemic treatment or second primary disease other than breast cancer in their follow up period. Citation Format: Gilseong Moon, Ji wool Ko, Hany Noh, In-Jeong Cho, Jong-in Lee, Airi Han. Poor prognosis in elderly patients with breast cancer resulted from under-treatment in patients with triple negative breast cancer and mortality from other than breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-72.
The Limitations of Pain Scales
Authors: Carlo V. Bellieni
Journal: JAMA Pediatrics (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
CD244 represents a new therapeutic target in head and neck squamous cell carcinoma
Authors: Laura Agresta, Maria Lehn, Kristin Lampe, Rachel Cantrell, Cassandra Hennies, Sara Szabo, Trisha Wise-Draper, Laura Conforti, Kasper Hoebe, Edith M Janssen
Journal: Journal for ImmunoTherapy of Cancer (2020)

Developing novel strategies to overcome the immunosuppressive tumor microenvironment is a critically important area of cancer therapy research. Here, we assess the therapeutic potential of CD244 (2B4/signaling lymphocyte activation molecule family 4), an immunoregulatory receptor found on a variety of immune cells, including exhausted CD8
Abstract 19645: Cardiac Effects of Physiological Hypertrophy in a Murine Model of Calcium Channel Overexpression
Authors: Larry Barr, Hongyu Zhang, Remus Berretta, Jeffery D Molkentin, Steven R Houser
Journal: Circulation (2012)

Background — The L-type calcium channel (LTCC) is integral for calcium entrance into the cardiomyocyte to induce CICR from the SR. We have developed a mouse model with inducible, cardiac-specific expression of the β2a subunit of the LTCC (β2a), leading to pathological hypertrophy akin to post-MI heart failure. Chronic exercise is known to cause physiological hypertrophy in normal hearts, leading to enhanced contractile state and thickened heart tissue, without a pathological phenotype. We administered chronic physiological hypertrophy in the form of swim training on the β2a line and its WT counterpart, analyzing the cardiac changes. Methods and Results — β2a (n=8) and WT (n=16) FVB mice aged 4 months were swam twice a day, four hours apart, for 21 days. They swam for 10min sessions on Day 1, with each subsequent day increasing the session time by 10 min until 90min sessions were reached. ECHO was performed at beginning and end of swim training, then terminal HW/BW ratio was determined. EF and FS increased significantly with swimming in WT (EF [%] pre-swim: 57.21±2.02 vs. post-swim: 69.98±2.88; FS [%] pre-swim: 29.53±1.34 vs. post-swim: 39.27±2.42) and from sedentary counterparts. β2a mice showed no significant change after swimming (EF [%] pre-swim: 69.8±1.75 vs. post-swim: 74.06±2.72; FS [%] pre-swim: 38.24±2.38 vs. post-swim: 42.40±2.22) and no change from sedentary β2a mice. Both ECHO parameters were significantly greater in β2a mice versus WT before swimming, but not after. There was a significant difference in HW/BW ratio in WT exercised mice versus sedentary (HW/BW [mg/g] swim: 4.63±0.2 vs. sed: 5.75±0.19) that was not present in exercised versus sedentary β2a mice (HW/BW [mg/g] swim: 5.98±0.31 vs. sed: 5.96±0.25). Conclusions — Chronic exercise may not affect mice with pathological hypertrophy through overexpressed LTCC but causes physiological hypertrophy in their wild type counterparts.
18FDG PET/CT in Primary Cutaneous Diffuse Large B-Cell Lymphoma Leg Type
Authors: Sébastien Dejust, David Morland, Eric Durot, Florent Grange, Dimitri Papathanassiou
Journal: Clinical Nuclear Medicine (2020)

Abstract An 86-year-old woman was referred for a rare but aggressive subtype of primary cutaneous lymphoma of the right lower limb: diffuse large B-cell lymphoma leg type. Initial evaluation by whole-body 18 F-FDG PET/CT showed intense hypermetabolic activity of multiple cutaneous and subcutaneous nodules of the distal third of the right leg. Follow-up evaluations by 18 F-FDG PET/CT showed complete response after 4 and 8 cycles of appropriate rituximab combination with polychemotherapy. Although no specific recommendations are available, our case stresses the major role of 18 F-FDG PET/CT for initial extension and treatment response evaluation in clinical practice of primary cutaneous diffuse large B-cell lymphoma leg type.
Integrin α6 mediates the drug resistance of acute lymphoblastic B-cell leukemia
Authors: Eun Ji Gang, Hye Na Kim, Yao-Te Hsieh, Yongsheng Ruan, Heather A. Ogana, Solomon Lee, Jennifer Pham, Huimin Geng, Eugene Park, Lars Klemm, Cheryl L. Willman, William L. Carroll, Steven D. Mittelman, Etan Orgel, Matthew J. Oberley, Chintan Parekh, Hisham Abdel-Azim, Deepa Bhojwani, Alan S. Wayne, Adèle De Arcangelis, Elisabeth Georges-Labouesse, Elizabeth Wayner, Halvard Bonig, Aspram Minasyan, Johanna ten Hoeve, Thomas G. Graeber, Markus Müschen, Nora Heisterkamp, Yong-Mi Kim
Journal: Blood (2020)
Abstract P4-12-08: Evaluation of acute toxicity in triple negative breast cancer patients receiving concurrent capecitabine and radiation
Authors: Chirag Modi, Zeinab Abou Yehia, Bruce Haffty
Journal: Cancer Research (2020)

Abstract Purpose: The addition of capecitabine is shown to improve survival in patients with Triple Negative Breast Cancer (TNBC). Administration of adjuvant capecitabine and radiation therapy sequentially after surgery for TNBC patients prolongs the time from surgery to radiation treatment. The purpose of this study was to evaluate the rate of acute loco-regional toxicity in patients with triple negative breast cancer who received concurrent adjuvant capecitabine and radiation. Materials and Methods: We performed a retrospective chart review of all patients diagnosed with breast cancer who were treated with capecitabine and radiation therapy at the Rutgers Cancer Institute of New Jersey between January 2010 and January 2019. Patients who had a previous radiation treatment course, hormone-receptor positive breast cancer and patients who received treatment sequentially were excluded. A total of 11 patients with TNBC who received concurrent capecitabine and RT were identified. Patient demographics, disease characteristics, radiation and capecitabine details, toxicity profile and treatment breaks were recorded. Toxicity was scored by the Common Terminology Criteria for Adverse Events version 5. Results: Median age was 52 years [34- 65]. Median Follow up from last Radiation treatment was 12 months [1- 63]. All patients had locally advanced disease and were treated with neoadjuvant chemotherapy. Adjuvant capecitabine dose ranged between 1000-3000 mg daily concurrent with a definitive course of radiation treatment ranging between 45 Gy- 50.4 Gy followed by an additional 10-14 Gy boost. All patients received radiation to the elective regional lymph nodes. Grade 1 or 2 radiation dermatitis was seen in all patients (11/11). Of the 11 patients, 2 patients (18%) experienced Grade 3 radiation dermatitis within the treatment field. One of these patients had a one week treatment break in which capecitabine was withheld; she then continued to a reduced boost dose. The second patient had grade 3 moist desquamation after completion of her radiation dose. No grade 4 or 5 toxicities were reported. In 10/11 (91%) patients had grade 1 or 2 skin hyperpigmentation. In 2 of the 11 patients, capecitabine was held at one point during treatment. Conclusion: Our study revealed an acceptable toxicity profile of receiving concurrent capecitabine and RT. These data support future prospective evaluation of this approach. Citation Format: Chirag Modi, Zeinab Abou Yehia, Bruce Haffty. Evaluation of acute toxicity in triple negative breast cancer patients receiving concurrent capecitabine and radiation [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-08.
Aldosterone-induced hypertension is sex-dependent, mediated by T cells and sensitive to GPER activation
Authors: Quynh Nhu Dinh, Antony Vinh, Hyun Ah Kim, Narbada Saini, Brad R S Broughton, Sophocles Chrissobolis, Henry Diep, Courtney P Judkins, Grant R Drummond, Christopher G Sobey
Journal: Cardiovascular Research (2020)

The G protein-coupled estrogen receptor 1 (GPER) may modulate some effects of aldosterone. In addition, G-1 (a GPER agonist) can lower blood pressure (BP) and promote T cell-mediated anti-inflammatory responses. This study aimed to test the effects of G-1 and G-15 (a GPER antagonist) on aldosterone-induced hypertension in mice and to examine the cellular mechanisms involved.
Regional Differences in Human Biliary Tissues and Corresponding In Vitro–Derived Organoids
Authors: Casey A. Rimland, Samantha G. Tilson, Carola M. Morell, Rute A. Tomaz, Wei‐Yu Lu, Simone E. Adams, Nikitas Georgakopoulos, Francisco Otaizo‐Carrasquero, Timothy G. Myers, John R. Ferdinand, Richard L. Gieseck, Fotios Sampaziotis, Olivia C. Tysoe, Alexander Ross, Judith M. Kraiczy, Brandon Wesley, Daniele Muraro, Matthias Zilbauer, Gabriel C. Oniscu, Nicholas R.F. Hannan, Stuart J. Forbes, Kourosh Saeb‐Parsy, Thomas A. Wynn, Ludovic Vallier
Journal: Hepatology (2020)

Background and Aims Organoids provide a powerful system to study epithelia in vitro . Recently, this approach was applied successfully to the biliary tree, a series of ductular tissues responsible for the drainage of bile and pancreatic secretions. More precisely, organoids have been derived from ductal tissue located outside (extrahepatic bile ducts; EHBDs) or inside the liver (intrahepatic bile ducts; IHBDs). These organoids share many characteristics, including expression of cholangiocyte markers such as keratin (KRT) 19. However, the relationship between these organoids and their tissues of origin, and to each other, is largely unknown. Approach and Results Organoids were derived from human gallbladder, common bile duct, pancreatic duct, and IHBDs using culture conditions promoting WNT signaling. The resulting IHBD and EHBD organoids expressed stem/progenitor markers leucine‐rich repeat–containing G‐protein‐coupled receptor 5/prominin 1 and ductal markers KRT19/KRT7. However, RNA sequencing revealed that organoids conserve only a limited number of regional‐specific markers corresponding to their location of origin. Of particular interest, down‐regulation of biliary markers and up‐regulation of cell‐cycle genes were observed in organoids. IHBD and EHBD organoids diverged in their response to WNT signaling, and only IHBDs were able to express a low level of hepatocyte markers under differentiation conditions. Conclusions Taken together, our results demonstrate that differences exist not only between extrahepatic biliary organoids and their tissue of origin, but also between IHBD and EHBD organoids. This information may help to understand the tissue specificity of cholangiopathies and also to identify targets for therapeutic development.
Socioeconomic gradient in health and the covid-19 outbreak
Authors: Roger Yat-Nork Chung, Dong Dong, Minnie Ming Li
Journal: BMJ (2020)

At the time of writing [1 April 2020], there have been 859 556 confirmed cases of covid-19 and 42 332 deaths.1 The epidemic has so far been controlled partially by national mobilisation of healthcare resources, but shortage of resources is of grave concern in other, especially developing, countries affected later by covid-19, underscoring global health inequalities.2

Many countries are currently using a household …
Abstract OT2-01-05: A prospective real-world national study to evaluate the efficacy and safety of adjuvant biosimilar trastuzumab in the treatment of HER2-positive breast cancer
Authors: Leandro Alves, Débora Gagliato, Mayara de Paula, Ana Carolina Cardoso, Alexandre Alcantara, Maristela Precivale, Vivienne Castilho
Journal: Cancer Research (2020)

Abstract Background: Treatment with anti-HER2 therapy significantly improved survival outcomes in patients with HER2-positive Breast Cancer (BC). In Brazil, Trastuzumab was the first biosimilar approved in the treatment of patients with breast (any disease setting) and advanced gastric cancer with overexpression of HER2. Increase access to this important treatment may be enhanced with biosimilar approval. The aim of this Real-World study is to assess the efficacy and safety of adjuvant biosimilar trastuzumab in Brazilian patients with early HER2+ BC. Methods: This is a national, multicenter, observational prospective, real-world study in a variety of Brazilian institutions. A hundred and seventy adult patients, with diagnosis of early stage HER2-positive breast cancer, who received at least one dose of biosimilar trastuzumab (Zedora) as adjuvant therapy will be included. Patients will be followed for 5 years after the use of biosimilar trastuzumab (Zedora), unless recurrence or death. Safety outcomes will be recorded. Efficacy outcomes include invasive relapse-free survival (IRFS) rate at 18, 24, 30 and 36 months treatment initiation. Given the inexistence of a specific hypothesis to be tested, sample size was based on the accuracy of the two-sided 95% confidence interval (95% CI) for the invasive disease relapse-free survival rate. Results: In development countries such as as Brazil, oncology treatments with biological drugs have high costs and represent an import ibarrier to patients access to anti HER2 therapy. The use of biosimilars may result in significant health care savings. Conclusions: Considering the HERITAGE study, in which biosimilarity was clearly demonstrated between the reference monoclonal antibody and the biosimilar, we do expect to find the same safety and efficacy profile. Citation Format: Leandro Alves, Débora Gagliato, Mayara de Paula, Ana Carolina Cardoso, Alexandre Alcantara, Maristela Precivale, Vivienne Castilho. A prospective real-world national study to evaluate the efficacy and safety of adjuvant biosimilar trastuzumab in the treatment of HER2-positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-01-05.
Abstract P1-19-28: Genomic screening reveals UBA1 as a potent and druggable target in diverse models of triple negative breast cancer
Authors: Sheeba Jacob, Tia H. Turner, Ann K. Yu, Colin M. Coon, Mohammad A. Alzubi, Charles T. Jakubik, Ynes Bouck, Mikhail G. Dozmorov, Sosipatros A. Boikos, Jennifer Koblinski, Joshua C. Harrell, Cyril H. Benes, Carlotta Costa, Anthony C. Faber
Journal: Cancer Research (2020)

Abstract Triple negative breast cancer (TNBC) confers the poorest prognosis of the major subtypes of breast cancers, and often inflicts young, African-American and Hispanic women. Steadily improving survival in other subsets of breast cancers are attributed to the implementation of effective targeted therapies, which are non-chemotherapy drugs that target a specific gene in a cancer. For instance, hormone positive BCs are treated effectively with anti-hormone targeted therapy, and HER2 amplified BCs are treated effectively with anti-HER2 targeted therapy. The CRISPR/CRISPR-associated protein-9 nuclease (Cas9) system, which enables specific gene editing to occur throughout the genome, allows for broad and unbiased discovery of new drug targets. We took advantage of this system to ask whether it may identify new druggable targets to treat TNBC and performed whole genome CRISPR/cas9 screening in two TNBC cell lines, BT549 and MDA-MB-468. To account for the heterogeneity found in TNBC, we further expanded the screen into seven other TNBC cell lines, by focusing on a select number of hits from the initial screen. This helped us identify a novel druggable target in TNBC, the ubiquitin activating enzyme 1 (UBA1). We took advantage of a recently reported small molecule inhibitor of UBA1, TAK-243, which is already in clinical trial evaluation in hematological cancers. Characterization of TAK-243 in cell culture models of TNBC and ex-vivo patient-derived xenografts (PDXs) demonstrated nanomolar IC50 toxicity, which was significantly lower than for tissue-derived normal cells. Mechanistically, TAK-243 therapy induced ER stress and the unfolded protein response in TNBC both in vitro and in vivo, leading to upregulation of activation transcription factor 4 (ATF4) and ATF6. Blocking ATF4 led to loss of NOXA and TAK-243 efficacy. TAK-243 induced tumor regressions in two PDX models of TNBC. Overall, these data demonstrate UBA1 is a novel drug target in TNBC. Citation Format: Sheeba Jacob, Tia H. Turner, Ann K. Yu, Colin M. Coon, Mohammad A. Alzubi, Charles T. Jakubik, Ynes Bouck, Mikhail G. Dozmorov, Sosipatros A. Boikos, Jennifer Koblinski, Joshua C. Harrell, Cyril H. Benes, Carlotta Costa, Anthony C. Faber. Genomic screening reveals UBA1 as a potent and druggable target in diverse models of triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-28.
Single-center results of visceral vascular resection for surgical treatment of patients with intrahepatic cholangiocarcinoma
Authors: Oleg Kotenko, Oleksii Popov, Oleksander Korshak, Oleksander Grinenko, Denis Fedorov, Andrii Husiev, Marat Grigorjan, Oleksander Ostapishen, Andrii Zhylenko
Journal: International Journal of Surgery (2020)