tbuckley/cabot-search huggingface dataset:
ALK actionable mutations (muts) within cancer types and their responses to crizotinib (CZ).
Authors: Lin Li, Caixia Liu, Jun Zhao, Lin Gen, Xiaorong Dong, Fenglei Yu, Xinghao Ai, Dongning Huang, Likun Chen, Xiangyang Cheng, Jinliang Kong, Renhua Guo, Liyun Miao, Li Lin, Li Liu, Gui Huang, Qiaoli Wang, Rongrong Chen, Xuefeng Xia
Journal: Journal of Clinical Oncology (2019)

e14739 Background: CZ was recommended by NCCN for ALK-rearranged metastasis NSCLC as first-line therapy. Knowledge on the occurrence of ALK actionable muts within cancer types and the responses of ALK fusion types to CZ could better guide the treatment of ALK-rearranged pts. Methods: 772 ALK-mutated pts (with any ALK muts) detected by tissue/ctDNA NGS in our institution from Oct. 2016 to Oct. 2018 were included. ALK + (with any ALK actionable muts) and EGFR - (with no EGFR actionable muts) pts treated with CZ at any line were included for survival analysis. Progress-free survival (PFS) was estimated using Kaplan-Meier method and compared using log-rank test. Results: 339 ALK + pts were analyzed, including 331 lung cancer (LC: 265 NSCLC; 1 SCLC; 65 Unknown histology), 3 brain cancer (BC), 1 colon cancer (CC), 3 cancer of unknown primary (CUP), and 1 with no clinical information. The most common ALK mut was fusion (331/339), including 315 EML4-ALK, 5 KIF5B-ALK, 4 STRN-ALK, 1 ACSL3-ALK, 1 CLIP4-ALK, 1 DCTN1-ALK, 1 HIP1-ALK, 1 SRBD1-ALK, 1 TFG-ALK, and 1 ZFP161-ALK. Fusion position was known for 308 EML4-ALK, including 132 V1, 108 V3, 32 V2, 19 V5’, and 17 other variants (Vx). Except for 2 V1 with CUP, 1 KIF5B-ALK with CUP, 1 Vx with CC, and 1 EML4-ALK (no variant information) with BC, all the other fusions occurred in LC. ALK F1174L was detected only in 2 pts, both of whom had BC, specifically neuroblastoma. CZ was given to 76 ALK + EGFR - pts (mPFS: 9 mo, 95% CI: 8 – 13), including 70 EML4-ALK and 6 non- EML4-ALK (mPFS: 10 vs. 9 mo, p = 0.7). Though non-significant, V1 (n = 32) on average had a longer mPFS than V3 (n = 28) (12 vs. 8 mo, p = 0.3), which may partially be explained by the younger age at diagnosis of V1 than V3 (48 vs. 53, p = 0.005). 1 TFG-ALK, 1 CLIP4-ALK, 1 DCTN1-ALK, 1 HIPI-ALK, 1 ZFP161-ALK, and 1 KIF5B-ALK achieved a PFS of 3, 4, 8, 9, 13, and 19 mo on CZ, respectively. 1 SCLC (V3) received CZ at first-line progressed after 6 mo. Conclusions: Though majority of the ALK actionable muts were commonly found in LC, some alterations may occur more often in other cancer types, such as F1174L in neuroblastoma. Some fusion types (e.g. TFG-ALK) may benefit less from CZ than others (e.g. KIF5B-ALK). Limited by relative small sample size, these results merit further validation and investigation.
A Large Retrospective Analysis of Pemetrexed (PEM) Activity in Patients (PTS) with Alk-Positive (Alk+) Non-Small Cell Lung Cancer (NSCLC) Prior to Crizotinib (CRIZ) Treatment
Authors: G. Scagliotti, D.W. Kim, A.T. Shaw, S.I. Ou, G.J. Riely, S. Gettinger, B. Besse, K. Wilner, Y. Tang, C.H. Bartlett
Journal: Annals of Oncology (2012)
Infected esophageal subepithelial hematoma after peroral endoscopic myotomy for achalasia successfully treated with double-pigtail stent drainage
Authors: Borathchakra Oung, Florian Rostain, Jérôme Rivory, André Boibieux, Armelle Schoch, François Mion, Mathieu Pioche
Journal: Endoscopy (2020)

Peroral endoscopic myotomy (POEM) has proven similarly effective to and less invasive than laparoscopic Heller myotomy and become the preferred option for the treatment of esophageal achalasia [1]. Few post-operative adverse events have been reported, among them a very low incidence of delayed bleeding causing a submucosal hematoma that could be treated with conservative management [2] [3].
Role of 68Ga–Prostate-Specific Membrane Antigen PET/CT in Disease Assessment in Glioblastoma Within 48 Hours of Surgery
Authors: Manoj Gupta, Partha Sarathi Choudhury, Ishwar Chandra Premsagar, Munish Gairola, Parveen Ahlawat
Journal: Clinical Nuclear Medicine (2019)

Abstract Within 48 hours after surgery, disease assessment in glioblastoma is a challenge for both the clinician and the radiologist. Certain technical and logistical issues prevail in this period. 68 Ga–prostate-specific membrane antigen PET/CT is a known molecular imaging marker in prostate cancer. Its role in high-grade gliomas has been recently discussed. We present a case of a 39-year-old man with recurrence glioblastoma of the right frontal lobe and underwent resurgery. After surgery, 68 Ga–prostate-specific membrane antigen PET/CT showed residual disease along the posterior and inferior margin of the postoperative cavity.
Staphylococcus aureus fibronectin-binding protein specifically binds IgE from atopic dermatitis patients and requires antigen presentation for cellular immune responses
Authors: K Reginald, K Westritschnig, B Linhart, M Focke-Tejkl, B Jahn-Schmid, A Heratizadeh, Angelika Stöcklinger, N Balice, S Spitzauer, T Werfel, Josef Thalhamer, S Weidinger, N Novakg, M Ollerth, A M Valenta Hirschl, R. Valenta
Journal: Journal of Allergy and Clinical Immunology (2011)
We need to improve postnatal care, starting with the maternal six week postnatal check
Authors: Judy Shakespeare, Cheryll Adams, Stephanie deGiorgio, Elizabeth Duff, Sarah Hillman, Judith Stephenson
Journal: BMJ (2020)

Jakes and colleagues’ paper on the maternal six week postnatal check is timely but anachronistic.1 Although not stated, this is aimed at general practitioners. A letter to the Guardian from four royal colleges2 and the Royal College of Obstetricians and Gynaecologists’ publication Better for Women also emphasise the need to improve care at this check.3 This is against a background of lack of …
Abstract 15153: Cardiac Electrical and Mechanical Synchrony of Peri-Left Bundle Branch Pacing
Authors: Jiangang Zou, Zeyu Jiang, Zhiyong Qian, Yuanhao Qiu, Xing Chen, Hai Jiang, Yao Wang, Xiaofeng Hou
Journal: Circulation (2018)

Introduction: Peri-left bundle branch (LBB) pacing is a novel pacing mode in the treatment of bradyarrhythmias. We aimed to evaluate electrical and mechanical synchrony in patients with peri-LBB pa...
First-in-Human, First-in-Child Trial of Autologous MSCs Carrying the Oncolytic Virus Icovir-5 in Patients with Advanced Tumors
Authors: David Ruano, José A. López-Martín, Lucas Moreno, Álvaro Lassaletta, Francisco Bautista, Maitane Andión, Carmen Hernández, África González-Murillo, Gustavo Melen, Ramón Alemany, Luis Madero, Javier García-Castro, Manuel Ramírez
Journal: Molecular Therapy (2020)

We present here the results of a first-in-human, first-in-child trial for patients with relapsed/refractory solid tumors using Celyvir, an advanced therapy medicine that combines autologous mesenchymal stem cells (MSCs) carrying an oncolytic adenovirus. Celyvir was manufactured from a bone marrow aspirate and then given intravenously. Patients received weekly infusions for 6 weeks at a dose of 2 × 106 cells/kg (children) or 0.5–1 × 106 cells/kg (adults), 2 × 104 viral particles per cell. Fifteen pediatric and 19 adult patients were recruited, but 18 were screen failures, mainly because rapid disease progression before Celyvir was available. No grade 2–5 toxicities were reported. Adenoviral replication detected by PCR was found in all but 2 pediatric patient and in none of the adult ones. Absolute numbers of circulating leukocytes suffered minor changes along therapy, but some subsets showed differences comparing the pediatric versus the adult cohorts. Two patients with neuroblastoma showed disease stabilization, and one of them continued on treatment for up to 6 additional weeks. Celyvir, the combination of MSCs and oncolytic adenovirus, is safe and warrants further evaluation in a phase 2 setting. The use of MSCs may be a strategy to increase the amount of oncolytic virus administered to patients, minimizing toxicities and avoiding direct tumor injections. We present here the results of a first-in-human, first-in-child trial for patients with relapsed/refractory solid tumors using Celyvir, an advanced therapy medicine that combines autologous mesenchymal stem cells (MSCs) carrying an oncolytic adenovirus. Celyvir was manufactured from a bone marrow aspirate and then given intravenously. Patients received weekly infusions for 6 weeks at a dose of 2 × 106 cells/kg (children) or 0.5–1 × 106 cells/kg (adults), 2 × 104 viral particles per cell. Fifteen pediatric and 19 adult patients were recruited, but 18 were screen failures, mainly because rapid disease progression before Celyvir was available. No grade 2–5 toxicities were reported. Adenoviral replication detected by PCR was found in all but 2 pediatric patient and in none of the adult ones. Absolute numbers of circulating leukocytes suffered minor changes along therapy, but some subsets showed differences comparing the pediatric versus the adult cohorts. Two patients with neuroblastoma showed disease stabilization, and one of them continued on treatment for up to 6 additional weeks. Celyvir, the combination of MSCs and oncolytic adenovirus, is safe and warrants further evaluation in a phase 2 setting. The use of MSCs may be a strategy to increase the amount of oncolytic virus administered to patients, minimizing toxicities and avoiding direct tumor injections.
A Tribute to Robert Roy Henry—The Classic “Academic Triple Threat”: Accomplished Researcher, Inspiring Teacher, and Compassionate Clinician
Authors: Steven Edelman, Jerrold Olefsky, Sunder Mudaliar, Ted Ciaraldi, Alain Baron
Journal: Diabetes Care (2020)

Robert (Bob) Roy Henry was born 12 March 1950 in Winnipeg, Manitoba, Canada, to Ken and Paula (nee Baldwin) Henry. His father was a train engineer and his mother a homemaker from Kent, England. Bob was raised in Transcon, a small town outside the city where most people joined the railway to make a living, and that is what his future looked like also. Bob and his wife, Denine McBeth, first met as teenagers. She was 16 and a cheerleader from a rival high school; he was 17 and owned a motorcycle.



Robert R. Henry, MD



The year following high school graduation he was able to find work at Manitoba Steel as a laborer. It was this experience that convinced him to pursue his education at the University of Winnipeg. Bob had a natural thirst for knowledge and thrived in the academic environment. During the course of his studies, he was in line for an academic excellence award (Canada’s recognition of students with outstanding achievements). However, Bob knew it would require another year at the University of Winnipeg and his interests had changed. He decided against pursuing the academic distinction and instead applied to and was accepted at the University of Manitoba in the field of medicine in 1971, graduating in 1975.



Left panel: Bob at 4 years old; right panel: Bob at graduation from the University of Manitoba, 1975



In 1973 he and Denine were married, and 2 years later their first son, Ryan, was born. During that time he was the president of the interns and residents’ association of Manitoba. After he graduated, he thought seriously of pursuing a specialty in cardiology at the University of Manitoba Health Science Centre. Unfortunately, on 11 September 1976, Bob, Denine, and Ryan were involved in a serious car accident that left …
US Organ Donation Policy
Authors: Raymond J. Lynch, David S. Goldberg
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
SDH5 Depletion Enhances Radiosensitivity by Regulating p53: A New Method for Noninvasive Prediction of Radiotherapy Response
Authors: Yan Zong, Qianwen Li, Furong Zhang, Xunde Xian, Sihua Wang, Jiahong Xia, Jie Li, Zhan Tuo, Guangqin Xiao, Li Liu, Guiling Li, Sheng Zhang, Gang Wu, Jun Liu
Journal: Theranostics (2019)

Radiotherapy is an effective treatment for lung cancer but lacks a reliable prediction method. Cell-free nucleic acids in plasma have been reported as a novel tumor marker. Here, we evaluate circulating succinate dehydrogenase 5 (SDH5) mRNA in plasma and SDH5 protein in tumors, assess their predictive value in lung cancer patients undergoing radiotherapy, and explore the underlying mechanisms. Methods: SDH5 expression was measured in peripheral blood samples and fresh tumor specimens from 208 non-small cell lung cancer (NSCLC) patients and correlated with clinical outcomes. SDH5 knockout mice and human xenograft mice were used to evaluate radiosensitivity. Cell growth, apoptosis, and the DNA damage response were assessed. Relevant RNA and protein levels were analyzed by qRT-PCR and Western blotting. Immunoprecipitation and GST pulldown assays were performed to detect protein-protein interactions. Polyubiquitination of p53 was examined by an in vitro ubiquitination assay. Results: Plasma and tumor SDH5 mRNA levels were positively correlated (rho=0.894, P<0.001). Patients with relatively low SDH5 levels in plasma (0.47, 0.12-0.89) and tumors (3.85, 0.96-7.23) had a better prognosis after radiotherapy (median PFS: 30.0 versus 15.0 months, hazard ratio: 0.276, 95% CI: 0.201-0.379, P<0.001). In SDH5 knockout mice, the lung epithelial cells exhibited increased DNA damage after radiation. In human lung xenograft mice, SDH5-deficient tumors had a smaller volume after radiotherapy. Furthermore, SDH5 depletion inhibits p53 degradation via the ubiquitin/proteasome pathway, which promotes apoptosis and enhances radiosensitivity in NSCLC. Conclusion: Our findings provide a novel noninvasive method for prediction of response to radiotherapy and may have significant implications for cancer radiotherapy.
Enabling Precision Oncology Through Precision Diagnostics
Authors: Noah A. Brown, Kojo S.J. Elenitoba-Johnson
Journal: Annual Review of Pathology Mechanisms of Disease (2020)

Genomic testing enables clinical management to be tailored to individual cancer patients based on the molecular alterations present within cancer cells. Genomic sequencing results can be applied to detect and classify cancer, predict prognosis, and target therapies. Next-generation sequencing has revolutionized the field of cancer genomics by enabling rapid and cost-effective sequencing of large portions of the genome. With this technology, precision oncology is quickly becoming a realized paradigm for managing the treatment of cancer patients. However, many challenges must be overcome to efficiently implement the transition of next-generation sequencing from research applications to routine clinical practice, including using specimens commonly available in the clinical setting; determining how to process, store, and manage large amounts of sequencing data; determining how to interpret and prioritize molecular findings; and coordinating health professionals from multiple disciplines.
“Hot Lung” Sign in Pulmonary Intravascular Large B-Cell Lymphoma on 18F-FDG PET/CT
Authors: Özlem Şahin, Buğra Kaya, Mustafa Serdengeçti, Hilal Akay Çizmecioğlu, Ahmet Eren Şen
Journal: Clinical Nuclear Medicine (2020)

Intravascular large B-cell lymphoma is a rare type of non-Hodgkin lymphoma characterized by intravascular proliferation of clonal lymphocytes within the lumen of small vessels, which is often fatal. Diffuse FDG uptake in the lung without clear/evident CT findings, "hot lung," is quasi-pathognomonic for lung intravascular large B-cell lymphoma. In this report, we present the case of a 43-year-old man who was diagnosed as having intravascular lymphoma thanks to this rare finding.
The MEK5–ERK5 Kinase Axis Controls Lipid Metabolism in Small-Cell Lung Cancer
Authors: Sandra Cristea, Garry L. Coles, Daniel Hornburg, Maya Gershkovitz, Julia Arand, Siqi Cao, Triparna Sen, Stuart C. Williamson, Jun W. Kim, Alexandros P. Drainas, Andrew He, Laurent Le Cam, Lauren Averett Byers, Michael P. Snyder, Kévin Contrepois, Julien Sage
Journal: Cancer Research (2020)

Abstract Small-cell lung cancer (SCLC) is an aggressive form of lung cancer with dismal survival rates. While kinases often play key roles driving tumorigenesis, there are strikingly few kinases known to promote the development of SCLC. Here, we investigated the contribution of the MAPK module MEK5–ERK5 to SCLC growth. MEK5 and ERK5 were required for optimal survival and expansion of SCLC cell lines in vitro and in vivo. Transcriptomics analyses identified a role for the MEK5–ERK5 axis in the metabolism of SCLC cells, including lipid metabolism. In-depth lipidomics analyses showed that loss of MEK5/ERK5 perturbs several lipid metabolism pathways, including the mevalonate pathway that controls cholesterol synthesis. Notably, depletion of MEK5/ERK5 sensitized SCLC cells to pharmacologic inhibition of the mevalonate pathway by statins. These data identify a new MEK5–ERK5–lipid metabolism axis that promotes the growth of SCLC. Significance: This study is the first to investigate MEK5 and ERK5 in SCLC, linking the activity of these two kinases to the control of cell survival and lipid metabolism.
Increased FDG Uptake on Juxtaglomerular Cell Tumor in the Left Kidney Mimicking Malignancy
Authors: Yuanyuan Jiang, Guozhu Hou, Zhaohui Zhu, Jinfeng Zang, Wuying Cheng
Journal: Clinical Nuclear Medicine (2019)

Abstract Juxtaglomerular cell tumor is a rare and benign tumor arising from the juxtaglomerular apparatus that overproduces renin, resulting in secondary hypertension. A 29-year-old woman was incidentally found to have a left renal mass by ultrasonography in a routine health examination. Contrast-enhanced CT results suggested renal cell carcinoma. FDG PET/CT performed for metastatic workup showed increased FDG uptake to the left renal mass and did not reveal any other abnormal FDG-avid lesions. The renal mass was surgically resected and pathological examination confirmed the juxtaglomerular cell tumor of the left kidney.
Everolimus and Octreotide for Patients with Recurrent Meningioma: Results from the Phase II CEVOREM Trial
Authors: Thomas Graillon, Marc Sanson, Chantal Campello, Ahmed Idbaih, Matthieu Peyre, Hadrien Peyrière, Noémie Basset, Didier Autran, Catherine Roche, Michel Kalamarides, Pierre-Hugues Roche, Stéphane Fuentes, Emeline Tabouret, Maryline Barrie, Anita Cohen, Stéphane Honoré, Mohamed Boucekine, Karine Baumstarck, Dominique Figarella-Branger, Anne Barlier, Henry Dufour, Olivier Louis Chinot
Journal: Clinical Cancer Research (2020)

Aggressive meningiomas that progress after surgery/radiotherapy represent an unmet medical need. Strong and constant expression of SSTR2A receptors and activation of the Pi3K/Akt/mTOR pathway have been demonstrated in meningiomas. The combination of everolimus, an mTOR inhibitor, and octreotide, a somatostatin agonist, has shown additive antitumor effect in vitro. The phase II CEVOREM trial investigated the efficacy of this combination on recurrent meningiomas.Patients with documented recurrent tumor progression ineligible for further surgery/radiotherapy were eligible to receive octreotide (30 mg/d, day 1) and everolimus (10 mg/d, days 1-28). The primary endpoint was the 6-month progression-free survival rate (PFS6). The secondary endpoints were overall survival, response rate, tumor growth rate according to central review, and safety.A total of 20 patients were enrolled, including 2 with World Health Organization (WHO) grade I tumors, 10 with WHO grade II tumors, and 8 with WHO grade III tumors; furthermore, 4 patients harbored NF2 germline mutation. The overall PFS6 was 55% [95% confidence interval (CI), 31.3%-73.5%], and overall 6- and 12-month survival rates were 90% (95% CI, 65.6%-97.4%) and 75% (95% CI, 50.0%-88.7%), respectively. A major decrease (>50%) was observed in the growth rate at 3 months in 78% of tumors. The median tumor growth rate decreased from 16.6%/3 months before inclusion to 0.02%/3 months at 3 months (P < 0.0002) and 0.48%/3 months at 6 months after treatment (P < 0.0003).The combination of everolimus and octreotide was associated with clinical and radiological activity in aggressive meningiomas and warrants further studies. Decrease in the tumor volume growth rate should be considered a complementary and sensitive endpoint to select potentially effective drugs for recurrent meningiomas.
B40 IGF-Binding Protein-Mediated Sensitization of EGFR-Mutant NSCLC Cells to Osimertinib by Cancer-Associated Fibroblast
Authors: L.L. Remsing Rix, N.J. Sumi, A.T. Bryant, B. Desai, X. Li, E.A. Welsh, B. Fang, B.M. Kuenzi, S.J. Antonia, C.M. Lovly, J.M. Koomen, A. Marusyk, E.B. Haura, U. Rix
Journal: Journal of Thoracic Oncology (2020)
Updated Safety and Quality of Life (QOL) Results of Paramount Study: Maintenance Pemetrexed (PEM) Plus Best Supportive Care (BSC) vs Placebo (PBO) Plus Bsc Immediately Following Induction Treatment with Pem Plus Cisplatin (CP) for Advanced Nonsquamous Non-Small Cell Lung Cancer (NS-NSCLC)
Authors: J. Pujol, L. Paz-Ares, M. Dediu, M. Thomas, P. Bidoli, J. Corral, N. Chouaki, C.M. Visseren-Grul, A. Zimmermann, C. Gridelli
Journal: Annals of Oncology (2012)
Just because it walks like a duck, quacks like a duck, doesn't mean it can't be a goose!
Authors: Nicolas Piliero, Adrien Jankowski, Frédéric Thony, Bruno Degano, Hélène Bouvaist
Journal: Thorax (2020)

The echocardiogram of a 62-year-old woman with a medical history of anti-synthetase syndrome associated with interstitial lung disease (ILD) suggested pulmonary hypertension. An etiological evaluation of pulmonary hypertension was performed. The ventilation/perfusion scan had the aspect of perfusion defects with dissociation. The CT scan showed features of active ILD (basal and subpleural pulmonary infiltration with regular septal line thickening and ground glass-like opacities). After multidisciplinary discussion, the pulmonary hypertension was considered to be secondary to either chronic thromboembolic pulmonary hypertension (CTEPH) and/or ILD. It was decided (i) to initiate an oral anticoagulant (rivaroxaban) and (ii) to initiate intravenous cyclophosphamide plus oral corticosteroids. One year later, while the patient was still taking rivaroxaban, right heart catheterisation showed the persistence of pre-capillary pulmonary hypertension with …