tbuckley/cabot-search huggingface dataset:
Defects in the Exocyst-Cilia Machinery Cause Bicuspid Aortic Valve Disease and Aortic Stenosis
Authors: Diana Fulmer, Katelynn Toomer, Lilong Guo, Kelsey Moore, Janiece Glover, Reece Moore, Rebecca Stairley, Glenn Lobo, Xiaofeng Zuo, Yujing Dang, Yanhui Su, Ben Fogelgren, Patrick Gerard, Dongjun Chung, Mahyar Heydarpour, Rupak Mukherjee, Simon C. Body, Russell A. Norris, Joshua H. Lipschutz
Journal: Circulation (2019)

Bicuspid aortic valve (BAV) disease is a congenital defect that affects 0.5% to 1.2% of the population and is associated with comorbidities including ascending aortic dilation and calcific aortic valve stenosis. To date, although a few causal genes have been identified, the genetic basis for the vast majority of BAV cases remains unknown, likely pointing to complex genetic heterogeneity underlying this phenotype. Identifying genetic pathways versus individual gene variants may provide an avenue for uncovering additional BAV causes and consequent comorbidities.We performed genome-wide association Discovery and Replication Studies using cohorts of 2131 patients with BAV and 2728 control patients, respectively, which identified primary cilia genes as associated with the BAV phenotype. Genome-wide association study hits were prioritized based on P value and validated through in vivo loss of function and rescue experiments, 3-dimensional immunohistochemistry, histology, and morphometric analyses during aortic valve morphogenesis and in aged animals in multiple species. Consequences of these genetic perturbations on cilia-dependent pathways were analyzed by Western and immunohistochemistry analyses, and assessment of aortic valve and cardiac function were determined by echocardiography.Genome-wide association study hits revealed an association between BAV and genetic variation in human primary cilia. The most associated single-nucleotide polymorphisms were identified in or near genes that are important in regulating ciliogenesis through the exocyst, a shuttling complex that chaperones cilia cargo to the membrane. Genetic dismantling of the exocyst resulted in impaired ciliogenesis, disrupted ciliogenic signaling and a spectrum of cardiac defects in zebrafish, and aortic valve defects including BAV, valvular stenosis, and valvular calcification in murine models.These data support the exocyst as required for normal ciliogenesis during aortic valve morphogenesis and implicate disruption of ciliogenesis and its downstream pathways as contributory to BAV and associated comorbidities in humans.
Effect of epigenetic modifier-based combinations on efficacy in patients with peripheral T-cell lymphoma (PTCL): Deciphering impact of mutations in epigenetic operations on response.
Authors: Owen A. O'Connor, Lubomir Sokol, Andrei R. Shustov, Lorenzo Falchi, Jennifer Kimberly Lue, Francesca Montanari, Jennifer Amengual, Ahmed Sawas, Chanchung Deng, Karen Khan, Alice Jacobs, Aishling Rada, Hye A. Kim, Craig R. Soderquist, David Park, Daniel Menezes
Journal: Journal of Clinical Oncology (2019)

7565 Background: Recurring mutations in epigenetic functions in PTCL, coupled with marked activity of epigenetic drugs, raises a question regarding whether these mutations might portend greater vulnerability to one drug over another. For example, do mutations in genes governing DNA methylation suggest these patients might benefit from a hypomethylating (HMA) agent? Preclinical data from our group suggests marked synergism between histone deacetylase inhibitors (HDACi) and HMA, as well as HDACi and pralatrexate (PDX), irrespective of mutations in epigenetic genes. Phase 1 studies (romidepsin [R] plus PDX or R plus 5-azacytidine [Aza]) are completed, and the Phase 2 studies are near completion. This clinical trial scenario affords a unique opportunity to decipher the impact of a HMA on response as a function of TET2, IDH2, DNMT3 and other mutations in PTCL. Methods: Patients with R/R lymphoma were eligible for the phase 1, whereas the phase 2 only enrolled patients with PTCL, either R/R or treatment-naïve individuals. Exploratory endpoints included next generation sequencing (NGS) and methylation arrays. Results: In toto, 89 patients have been enrolled on both trials across all histology’s, 58 have PTCL. NGS and efficacy data is available for the majority of patients, with some from the PDX + R study in process. The ORR among the PTCL patients for PDX+R and Aza+R has been 71% and 73% respectively. Eight of 9 angioimmunoblastic TCL patients responded. Among those with TET2 mutations, 7 of 8 responded to the Aza based treatment, while only 3 of 6 (50%) who were TET2 negative responded. Similarly, of 3 patients with DNMT3 treated with Aza based therapy, all 3 responded. Remarkably one patient with a TET2 mutation experienced progression to PDX+R, and CR to Aza+R. Among the PTCL patients treated with Aza, the global demethylation score (GDMS) demonstrated marked demethylation among all patients, with no correlation between the score and likelihood of response. Conclusions: We will share the completely annotated analysis correlating clinical metrics to the spectrum of epigenetic mutations and GDMS and across all histology’s and treatments. Clinical trial information: NCT01998035; NCT01947140.
The regulatory mechanism involved in paclitaxel-induced apoptosis: The role of ATF-3 on apoptosis in cervical cancer cell line (HeLa cell)
Authors: Y. Kwon
Journal: Journal of Clinical Oncology (2007)

16052 Background: Paclitaxel, which is a potent anti-cancer drug and microtubule-binding agent, has been found to be effective against several tumors, including cervical cancer. However, the exact mechanism underlying the apoptotic effects of paclitaxel is poorly understood. Methods: We show that paclitaxel induces apoptosis, as demonstrated by DNA fragmentation, TUNEL assay, and flow cytometry analysis in cervical cancer HeLa cells, correlating with enhanced caspase-3 activation and p73 as well as p21, which are inhibited strongly by p73 siRNA. Results: The paclitaxel treatment followed by the overexpression of wild type ATF3 potentiated apoptosis is by enhancing p73 expression, but these events were attenuated in C-terminal deleted ATF3 or ATF3 siRNA-transfected cells. Interestingly, paclitaxel-induced ATF3 colocalizes with transfected GFP-p73 in nucleus, but not in p73 siRNA-transfected cells. Conversely, p73 may not affect ATF3 expression, as increase of ATF3 expression did not detect in p73-overexpressing cells. Furthermore, we observed that ATF3 binds to DNA binding domain of p73, confirmed by GST-pull down assay for ATF3. Additionally, ATF3 potentiates p21 gene, a downstream target of p73, promoter activity and p73-p21 binding activity induced by paclitaxel and also we have obtained similar data in the tissue of cervical cancer patient treated with paclitaxel. Conclusions: Collectively, these results demonstrate that overexpression of ATF3 potentiates paclitaxel-induced apoptosis in HeLa cells, at least in part, through stimulating the p73 expression and its transcriptional activity. ATF3 may function as a tumor-inhibiting factor by regulating directly p73 and may suggest a functional link between ATF3 and p73. No significant financial relationships to disclose.
Pik3ip1 Is a Negative Immune Regulator that Inhibits Antitumor T-Cell Immunity
Authors: Yichen Chen, Jun Wang, Xi Wang, Xinye Li, Jingjing Song, Juan Fang, Xiangqi Liu, Tao Liu, Dikan Wang, Qunxing Li, Shuqiong Wen, Da Ma, Juan Xia, Liqun Luo, Song Guo Zheng, Jun Cui, Gucheng Zeng, Lieping Chen, Bin Cheng, Zhi Wang
Journal: Clinical Cancer Research (2019)

Multiple negative regulators restrict the ability of T cells to attack tumors. This work demonstrates the role of PI3K-interacting protein 1 (Pik3ip1) in restraining T-cell responses and antitumor immunity.An anti-Pik3ip1 mAb was generated to identify the Pik3ip1 expression pattern of hematopoietic cells. Pik3ip1-/- mice and a Pik3ip1 fusion protein were generated to investigate the effect of Pik3ip1 on T-cell-mediated antitumor immunity in MC38 and B16-F10 tumor models. Immunoblotting and confocal microscopy were used to identify inhibitory effects of Pik3ip1 on T-cell receptor (TCR) signaling. Pik3ip1 expression was quantified, and its impact on T-cell function in human tumors was measured.We demonstrated that Pik3ip1 was predominantly expressed on T cells and served as an essential rheostat for T-cell-mediated immunity. A Pik3ip1 genetic deficiency led to enhanced T-cell responsiveness upon immunization with a neoantigen. Pik3ip1-/- mice exhibited a marked increase in antitumor immunity and were resistant to tumor growth. Furthermore, Pik3ip1 extracellular domain fusion protein enhanced MC38 tumor growth was observed. Mechanistically, we found that Pik3ip1 inhibited TCR signaling by mediating the degradation of SLP76 through Pik3ip1 oligomerization via its extracellular region. Consistent with the results from the mouse models, PIK3IP1 expression correlated with T-cell dysfunction in human tumors.Our data reveal a critical role for Pik3ip1 as a novel inhibitory immune regulator of T-cell responses and provide a potential molecular target for cancer immunotherapy.
Simplified LV5FU2-irinotecan (FOLFIRI) in the first-line therapy of well-differentiated endocrine carcinomas of the duodeno- pancreatic area: Preliminary results of the FFCD 0302 phase II trial with GTE participation
Authors: G. Cadiot, F. Bonnetain, B. Landi, O. Bouché, E. Mitry, L. Bedenne, P. Ruszniewski, F. Ricard, F. Vitry, J. L. Jouve
Journal: Journal of Clinical Oncology (2007)

4620 Introduction: Few chemotherapies have been tested in the first-line treatment of endocrine carcinomas. The aim of the study was to evaluate the efficacy of FOLFIRI in the first-line therapy of evolutive, metastatic or locally invasive, well-differentiated endocrine carcinomas of the duodeno-pancreatic area. Methods: To show a 6-month tumoral non-progression (RECIST) rate ≥ 60% (a = 5%), 20 pts had to be included in a phase II, prospective, multicentric trial. Inclusion criteria were : well-differentiated endocrine carcinoma of the duodeno-pancreatic area, functioning or non functioning, with hepatic or extra-hepatic metastases or locally invasive tumor &gt; 50 mm, not resectable; tumoral growth within 6 months; no previous antitumoral therapy except interferon ( = 3 months) or somatostatin analogs; PS 0–2. Treatment administration every 14 days : D1 : irinotecan 180 mg/m 2 , folinic acid 400 mg/m 2 , 5 FU 400 mg/m 2 bolus; D1-D2 : 5 FU 2,400 mg/m 2 in 46 hrs. Evaluation (clinical, radiological, biological) every 3 months. In case of progression during a chemotherapy free-interval following an objective tumoral response, treatment was reintroduced. All analyses were performed in intent to treat. Data cut off was done at July 1st 2006. Results: Between May 2004 and July 2005, 20 pts (13 M, 7 F) were included with median age 57 yrs (37–82). 19 pts had liver metastases and 1 pt had metastatic lymph nodes. 5 tumors were functioning; 2 pts had MEN 1. Median proliferation index was 7% (0–58). All pts were treated and evaluation at 6 months for the primary endpoint was available in 19 pts. The 6-month non-progression rate was 75% (CI 95% = 51–91%,), including 14 stabilization (70%) and 1 partial response (5%). 4 pts had 1 chemotherapy free-interval and 2 pts had 2 with reintroduction of the same chemotherapy regimen. Median number of cycles was 11.5 (1–28). 80% had at least 1 grade 3–4 toxicity and 25% had grade 3–4 hematological toxicity. 10% had grade 3 diarrhoea.. Conclusion: FOLFIRI has an antitumoral effect in the first-line therapy of evolutive well-differentiated pancreatic endocrine carcinomas. Frequency of grade 3–4 toxicities can be explained by length of therapy. No significant financial relationships to disclose.
Pathologic response, KRAS status, and bevacizumab: The Bermuda triangle for outcome prediction after hepatic colorectal cancer metastases (HCRM) resection.
Authors: Giuseppe Fanetti, Pamela Biondani, Anna Tessari, Flavia Melotti, Massimo Milione, Filippo G. De Braud, Federica Perrone, Rosalba Miceli, Luigi Mariani, Arpine Gevorgyan, Maria Di Bartolomeo, Filippo Pietrantonio
Journal: Journal of Clinical Oncology (2013)

e14716 Background: Clinicopathologic factors are insufficient to stratify prognosis after HCRM resection. The identification of prognostic biomarkers is an unmet clinical need. Even if the prognostic role of KRAS mutations in the metastatic setting is controversial, recent data hypothesized a correlation to worse outcome after HCRM resections. This analysis evaluated the correlation between KRAS mutation, pathological response and outcome. Methods: Fifty-eight pts with HCRM were resected at National Cancer Institute of Milan from 2007 to 2012 following bevacizumab (Bev) (n=30) or cetuximab (Cmab) (n=28) based neoadjuvant regimens. Tumor regression grade (TRG) was classified from TRG 1 for pathological complete response (pCR), to TRG5 for no response; TRG 1-3 for response; TRG 4-5 for scarce/no response. KRAS exons 2 to 4 were sequenced by direct PCR. Results: KRAS missing in 3 pts (1 Bev/2 Cmab), mutated in 23 (42%) vs wild-type in 32 (58%), mutated in 18 (62%) of Bev group vs 5 (19%) of Cmab. Mean TRG: 2.9 (2.2-4) in Bev vs 3.8 (3-5) in Cmab group (p=0.04 at Kruskal-Wallis test). Pathological response higher for Bev vs Cmab (70% vs 39%; p=0.037 at Chi-square test). Bev also increased pCRs (20% vs 0%, p=0.024 at Fisher’s test). Pathological response higher for KRAS mutant vs wild-type (70% vs 41%; p=0.003 at Chi-square test). At log-rank test, DFS significantly shorter for KRAS mutated vs wild-type (7.6 vs 14.6 months; p=0.05), and for TRG4-5 vs TRG1-3 (8.1 vs 15.3 months; p=0.02), while no difference observed according to treatment. OS data are not mature. Multivariable Cox model for DFS shown in the Table. Conclusions: After Bev-based neoadjuvant treatment, patients with KRAS mutated HCRM and without good pathological response may have the worst outcome after curative resection. [Table: see text]
Sex-Based Disparities Among Cancer Clinical Trial Participants
Authors: Ethan B Ludmir, C David Fuller, Shalini Moningi, Walker Mainwaring, Timothy A Lin, Austin B Miller, Amit Jethanandani, Andres F Espinoza, Vivek Verma, Benjamin D Smith, Grace L Smith, Noam A VanderWalde, Emma B Holliday, B Ashleigh Guadagnolo, Thomas E Stinchcombe, Reshma Jagsi, Daniel R Gomez, Bruce D Minsky, Claus Rödel, Emmanouil Fokas
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Landmark investigation two decades ago demonstrated sex-based disparities among participants in cancer cooperative group trials. Although federal efforts have aimed to improve representation of female patients in government-sponsored research, less is known about sex disparities in the broader landscape of modern oncologic randomized controlled trials. Using ClinicalTrials.gov, we identified randomized controlled trials related to colorectal or lung cancer (the two most common non-sex-specific disease sites). Among the 147 included trials, the proportion of female patients enrolled on trial was on average 6.8% (95% confidence interval = −8.8% to –4.9%) less than the proportion of female patients in the population by disease site (P &amp;lt; .001). Whereas no statistically significant underrepresentation of women was noted within the 26 cooperative group trials, sex disparities were markedly heightened for the 121 noncooperative-group-sponsored trials. Furthermore, underrepresentation of women did not improve with time. Future efforts should therefore focus on addressing these pervasive sex-based enrollment disparities beyond cooperative group trials alone.
Pneumocystis Jiroveci Pneunomia Prophylaxis during Maintenance Therapy with Hyper-CVAD Regimens for Adult Acute Lymphoblastic Leukemia
Authors: Grace A. Martin, Shilpa Paul, Wei Qiao, Elias J. Jabbour, Dimitrios P. Kontoyiannis, Deborah A. McCue
Journal: Blood (2017)
Fractures While Walking Leashed Dogs—Reply
Authors: Kevin Pirruccio, Jaimo Ahn
Journal: JAMA Surgery (2019)

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 Surgery 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 Surgery journal
Notch Signaling Promotes the Differentiation of Human CLEC9A+ Dendritic Cells from Hematopoietic Stem and Progenitor Cells
Authors: Christopher S. Seet, Suwen Li, Brent Chick, David Casero, Eric H. Gschweng, Yuhua Zhu, Runfeng Miao, Amelie Montel-Hagen, Donald B Kohn, Mary Sehl
Journal: Blood (2017)
Ptu-024 - photometric stereo reconstruction for surface analysis of mucosal tissue
Authors: Andy Poullis, Chris Groves, Greg Slabaugh, Khemraj Emrith, Melvyn Smith
Journal: BMJ (2015)

This paper provides a novel approach for real-time detection of polyps. Using a photometric stereo sensor for endoscopy imaging in a porcine model, the 3D surface geometry of a porcine gut is recovered. Shape features are extracted from the 3D surface data and analysed to detect and identify regions that are locally spherical, suggestive of polyps to aid polyp detection.
Abstract 10477: Adverse Functional Significance of Cardiac Beta3-Adrenergic Receptor Activation on Left Ventricular Contractile Performance in Conscious, Chronically-Instrumented Dogs With Pacing-Induced Heart Failure
Authors: Heng-Jie Cheng, Xiaowei Zhang, Tiankai Li, Zhi Zhang, Dwight D Deal, James E Jordan, Zhe Chen, David Herrington, John Adams, Che Ping Cheng
Journal: Circulation (2018)

Background: In heart failure (HF), the cardiac β3-adrenergic receptor (AR)-mediated inhibitory pathway is up-regulated, suggesting a contributing role of β3-AR activation on HF progression. However...
Economics of using telehospice to supplement hospice care in rural areas.
Authors: Adam Lomenick, Sandy Kuhlman, Tami Gurley-Calvez, Joe Barnes, Hope Krebill, Ashley Spaulding, Gary C. Doolittle
Journal: Journal of Clinical Oncology (2019)

11535 Background: Hospice care in rural areas is often characterized by provider shortages and vast geographical service areas to cover, making access to quality end-of-life care challenging. Telehospice, the utilization of interactive video (ITV) technology to provide health services over a distance for hospice patients, has been proposed as a solution to address access issues. In 2017, the University of Kansas Medical Center (Kansas City, Kansas) partnered with Hospice Services, Inc. (HSI) (Phillipsburg, Kansas) to augment traditional, in-person hospice care with hospice care delivered via mobile tablets.This work examines the costs of Telehospice when compared with the costs of in-person hospice services. Methods: Detailed administrative data from July 1, 2018 to December 31, 2018 was analyzed to estimate the costs of service after Telehospice use was inculcated into routine practice. Results: Hospice Services, Inc., which averages a daily census of 34 patients, conducted 257 calls, averaging 28 hours a month. The average time for a Telehospice call was 21 and 18 minutes for nursing and medical director calls, respectively. Through various hospice functions, including administrative, patient, and non-patient related connections, HSI saved over $115,000 in staff travel time and mileage reimbursement. Administratively, by hosting their weekly 14-member interdisciplinary meeting via ITV, HSI saved $29,869 of staff travel time and mileage reimbursement. Conclusions: Our estimates indicate substantial cost saving potential with the use of Telehospice services. Further research is needed to assess the effects of Telehospice utilization on the experiences and subsequent cost of hospice care. Additional cost data specifics will be presented in poster form. [Table: see text]
Engineering “cell-particle hybrids” of pancreatic islets and bioadhesive FK506-loaded polymeric microspheres for local immunomodulation in xenogeneic islet transplantation
Authors: Tiep Tien Nguyen, Tung Thanh Pham, Hanh Thuy Nguyen, Mahesh Raj Nepal, Cao Dai Phung, Zhiwei You, Nikita Katila, Nirmala Tillija Pun, Tae Cheon Jeong, Dong-Young Choi, Pil-Hoon Park, Chul Soon Yong, Jong Oh Kim, Simmyung Yook, Jee-Heon Jeong
Journal: Biomaterials (2019)
Atializumab, a humanized anti-aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1) antibody significantly improves nephritis in (NZB/NZW) F1 mice
Authors: Chin Hee Mun, Jin-Ock Kim, Sung Soo Ahn, Taejun Yoon, Su Jeong Kim, Eunhee Ko, Hee-Dong Noh, Yong-Beom Park, Hak-Jun Jung, Tae Sung Kim, Sang-Won Lee, Sang Gyu Park
Journal: Biomaterials (2019)
Results from a structured interprofessional palliative care rehabilitation program in oncology.
Authors: Martin Robert Chasen, Andrea Feldstain, Debbie Gravelle, Neil MacDonald, Jose Pereira
Journal: Journal of Clinical Oncology (2013)

e20598 Background: Post-treatment patients with active cancer face considerable burden from the effects of both disease and treatment. The Palliative Rehabilitation Program was designed to ease those challenges and to improve the patient’s functioning. The current study evaluated the changes in function scores of patients with advanced cancer upon completion of the structured program and examined the medical predictors of program completion. Methods: Referrals for 173 patients who were finished anticancer therapy were received. One hundred and thirty six patients were eligible and enrolled in the eight-week interprofessional palliative rehabilitation program. Of those, 84 completed the program. Measures of physical, nutritional, social and psychological functioning were evaluated at entry and completion of the program. Results: Significant improvements were experienced in physical performance (P =0.000), nutrition (P =0.000), symptom severity (P=0.005 to P= 0.000), symptom interference in functioning (P =0.001 to P=0.000), and fatigue (P=0.001 to P=0.000). Reasons for not completing the program were: disease progression, geographical inaccessibility, being too well, dying, and personal/unknown reasons. A normal CRP level (&lt;10mg/L; P=0.013) was a predictor of program completion. Conclusions: Patients living with advanced heterogeneous cancers who underwent an interprofessional palliative rehabilitation program experienced significant improvement in their functioning in many domains. Program completion can be predicted by normal CRP level.
Pheochromocytoma and Paraganglioma
Authors: Hartmut P.H. Neumann, William F. Young, Charis Eng
Journal: New England Journal of Medicine (2019)

Pheochromocytoma and paraganglioma are related tumors that differ mainly in location; pheochromocytomas are adrenal, and paragangliomas can be anywhere else. The symptoms are protean and common, but the tumors are rare. The diagnosis may signify an underlying genetic syndrome.
A Phase 1b Study to Assess the Combination of Selinexor and Daratumumab in Patients with Relapsed / Refractory Multiple Myeloma Previously Exposed to Proteasome Inhibitors (PI) and Immunomodulatory Drugs (IMiDs)
Authors: Cristina J. Gasparetto, Suzanne Lentzsch, Gary J Schiller, William Bensinger, Nizar J. Bahlis, Heather J. Sutherland, Darrell J White, Michael Sebag, Rami Kotb, Christopher P. Venner, Richard LeBlanc, Christine I Chen, Aldo Del Col, Michael G. Kauffman, Sharon Shacham, Jacqueline Jeha, Jean-Richard Saint-Martin, Jatin Shah, Brea C. Lipe
Journal: Blood (2017)