tbuckley/cabot-search huggingface dataset:
Serial ctDNA Monitoring to Predict Response to Systemic Therapy in Metastatic Gastrointestinal Cancers
Authors: Aparna R. Parikh, Amikasra Mojtahed, Jaime L. Schneider, Katie Kanter, Emily E. Van Seventer, Isobel J. Fetter, Ashraf Thabet, Madeleine G. Fish, Bezaye Teshome, Kathryn Fosbenner, Brandon Nadres, Heather A. Shahzade, Jill N. Allen, Lawrence S. Blaszkowsky, David P. Ryan, Bruce Giantonio, Lipika Goyal, Ryan D. Nipp, Eric Roeland, Colin D. Weekes, Jennifer Y. Wo, Andrew X. Zhu, Dora Dias-Santagata, A. John Iafrate, Jochen K. Lennerz, Theodore S. Hong, Giulia Siravegna, Nora Horick, Jeffrey W. Clark, Ryan B. Corcoran
Journal: Clinical Cancer Research (2020)

ctDNA offers a promising, noninvasive approach to monitor therapeutic efficacy in real-time. We explored whether the quantitative percent change in ctDNA early after therapy initiation can predict treatment response and progression-free survival (PFS) in patients with metastatic gastrointestinal cancer.A total of 138 patients with metastatic gastrointestinal cancers and tumor profiling by next-generation sequencing had serial blood draws pretreatment and at scheduled intervals during therapy. ctDNA was assessed using individualized droplet digital PCR measuring the mutant allele fraction in plasma of mutations identified in tumor biopsies. ctDNA changes were correlated with tumor markers and radiographic response.A total of 138 patients enrolled. A total of 101 patients were evaluable for ctDNA and 68 for tumor markers at 4 weeks. Percent change of ctDNA by 4 weeks predicted partial response (PR, P < 0.0001) and clinical benefit [CB: PR and stable disease (SD), P < 0.0001]. ctDNA decreased by 98% (median) and >30% for all PR patients. ctDNA change at 8 weeks, but not 2 weeks, also predicted CB (P < 0.0001). Four-week change in tumor markers also predicted response (P = 0.0026) and CB (P = 0.022). However, at a clinically relevant specificity threshold of 90%, 4-week ctDNA change more effectively predicted CB versus tumor markers, with a sensitivity of 60% versus 24%, respectively (P = 0.0109). Patients whose 4-week ctDNA decreased beyond this threshold (≥30% decrease) had a median PFS of 175 days versus 59.5 days (HR, 3.29; 95% CI, 1.55-7.00; P < 0.0001).Serial ctDNA monitoring may provide early indication of response to systemic therapy in patients with metastatic gastrointestinal cancer prior to radiographic assessments and may outperform standard tumor markers, warranting further evaluation.
Transarterial Infusion Chemotherapy with Cisplatin Plus S-1 for Treating Hepatocellular Carcinoma: Results of a Phase I Trial
Authors: T. Terazawa, S. Kondo, C. Morizane, T. Yamaguchi, S. Shimizu, M. Shuichi, M. Ikeda, H. Ueno, T. Okusaka
Journal: Annals of Oncology (2012)
Combined MEK and PI3K/p110β Inhibition as a Novel Targeted Therapy for Malignant Mesothelioma Displaying Sarcomatoid Features
Authors: Miriam Marqués, Robin Tranchant, Blanca Risa-Ebrí, María L. Suárez-Solís, Luis C. Fernández, Enrique Carrillo-de-Santa-Pau, Natalia del Pozo, Jaime Martínez de Villarreal, Clément Meiller, Yves Allory, Yuna Blum, Christine Pirker, Balazs Hegedus, Simon T. Barry, Amancio Carnero, Walter Berger, Didier Jean, Francisco X. Real
Journal: Cancer Research (2020)

Among malignant mesotheliomas (MM), the sarcomatoid subtype is associated with higher chemoresistance and worst survival. Due to its low incidence, there has been little progress in the knowledge of the molecular mechanisms associated with sarcomatoid MM, which might help to define novel therapeutic targets. In this work, we show that loss of PTEN expression is frequent in human sarcomatoid MM and PTEN expression levels are lower in sarcomatoid MM than in the biphasic and epithelioid subtypes. Combined Pten and Trp53 deletion in mouse mesothelium led to nonepithelioid MM development. In Pten;Trp53-null mice developing MM, the Gαi2-coupled receptor subunit activated MEK/ERK and PI3K, resulting in aggressive, immune-suppressed tumors. Combined inhibition of MEK and p110β/PI3K reduced mouse tumor cell growth in vitro. Therapeutic inhibition of MEK and p110β/PI3K using selumetinib (AZD6244, ARRY-142886) and AZD8186, two drugs that are currently in clinical trials, increased the survival of Pten;Trp53-null mice without major toxicity. This drug combination effectively reduced the proliferation of primary cultures of human pleural (Pl) MM, implicating nonepithelioid histology and high vimentin, AKT1/2, and Gαi2 expression levels as predictive markers of response to combined MEK and p110β/PI3K inhibition. Our findings provide a rationale for the use of selumetinib and AZD8186 in patients with MM with sarcomatoid features. This constitutes a novel targeted therapy for a poor prognosis and frequently chemoresistant group of patients with MM, for whom therapeutic options are currently lacking. SIGNIFICANCE: Mesothelioma is highly aggressive; its sarcomatoid variants have worse prognosis. Building on a genetic mouse model, a novel combination therapy is uncovered that is relevant to human tumors.
MDRを逆転するP-gp siRNAが仲介する多機能化ミセルによる化学感受性の修復 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Shen Jie, Wang Qiwen, HU Qida, LI Yongbing, Tang Guping, K Chu Paul
Journal: Biomaterials (2014)
Increased Myocardial Stiffness in Patients With High-Risk Left Ventricular Hypertrophy
Authors: Michinari Hieda, Satyam Sarma, Christopher M. Hearon, Katrin A. Dias, Jose Martinez, Mitchel Samels, Braden Everding, Dean Palmer, Sheryl Livingston, Margot Morris, Erin Howden, Benjamin D. Levine
Journal: Circulation (2019)

Background: Individuals with left ventricular hypertrophy (LVH) and elevated cardiac biomarkers in middle age are at high risk for the development of heart failure with preserved ejection fraction (HFpEF). However, it is unknown what the pathophysiological underpinnings of this high-risk state may be. We tested the hypothesis that patients with LVH and elevated cardiac biomarkers would demonstrate elevated left ventricular (LV) myocardial stiffness in comparison with healthy controls as a key marker for future HFpEF. Methods: Forty-six patients with LVH (LV septum &gt;11 mm) and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [&gt;40 pg/mL] or troponin T [&gt;0.6 pg/mL]) were recruited, along with 61 age- and sex-matched (by cohort) healthy controls. To define LV pressure-volume relationships, right heart catheterization and 3-dimensional echocardiography were performed while preload was manipulated using lower body negative pressure and rapid saline infusion. Results: There were significant differences in body size, blood pressure, and baseline pulmonary capillary wedge pressure between groups (eg, pulmonary capillary wedge pressure: LVH, 13.4±2.7 versus control, 11.7±1.7 mm Hg, P &lt;0.0001). The LV was less distensible in LVH than in controls (smaller volume for the same filling pressure). When preload was expressed as transmural filling pressure (pulmonary capillary wedge pressure – right atrial pressure), LV myocardial stiffness was nearly 30% greater in LVH than in controls (LVH stiffness constant, 0.053±0.027 versus controls, 0.042±0.020, P =0.028). Conclusions: LV myocardial stiffness in patients with LVH and elevated biomarkers (stage-B HFpEF) is greater than in age- and sex-matched controls and thus appears to represent a transitional state from a normal healthy heart to HFpEF. Although the LV myocardial stiffness of patients with LVH is greater than that of healthy controls at this early stage, further studies are required to clarify whether interventions such as exercise training to improve LV compliance may prevent the full manifestation of the HFpEF syndrome in these high-risk individuals. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT03476785 and NCT02039154.
Maternal Weight Trajectories in Successive Pregnancies and Their Association With Gestational Diabetes Mellitus
Authors: Ciara M.E. Reynolds, Eimer G. O’Malley, Brendan Egan, Sharon R. Sheehan, Michael J. Turner
Journal: Diabetes Care (2020)

Gestational diabetes mellitus (GDM) can have serious clinical consequences for both the woman and her offspring in the short and long term (1). Previous research suggests that an interpregnancy weight increase of just 1–2 BMI units is associated with an increased risk of the development of GDM in future pregnancies (2). However, BMI units may not be the most practical approach to addressing weight management (3). In the general population, international guidelines on weight management recommend percentage weight loss for use in clinical practice (4). This study aimed to determine if change in percentage body weight between the start of the first and second pregnancies was associated with the development of GDM in the second pregnancy.

This study was conducted using a database of all births in the Coombe Women and Infants University Hospital, Dublin, between 2011 and 2018 inclusive. Women who had first and second singleton babies weighing ≥500 g were included. Women whose weight was measured at >18 weeks’ gestation, who had preexisting diabetes, or who had a previous baby weighing >4.5 kg were excluded.

The hospital follows the International Association of Diabetes and …
A Diffuse Medullary Hypercaptation With No Bone Lesion
Authors: Alexia Christin, Laurence de Leval, Michel Obeid
Journal: JAMA Oncology (2020)

A 71-year-old man presented with a 3-year history of pericarditis and pleural effusions; imaging and biopsy results showed diffuse medullary hypercaptation in the bone marrow and spleen. What is your diagnosis?
Circulating Melanoma Cells (CMCS) in Mucosal and Uveal Melanomas
Authors: L.T. Khoja, P. Shenjere, S. Bramley, R. Milner, A. Kvist, R. Califano, G. Clack, A. Hughes, P. Lorigan, C. Dive
Journal: Annals of Oncology (2012)
Kappa Opioid Receptor Antagonists as Potential Therapeutics for Stress-Related Disorders
Authors: Moriah L. Jacobson, Caroline A. Browne, Irwin Lucki
Journal: The Annual Review of Pharmacology and Toxicology (2020)

Exposure to stressful stimuli activates kappa opioid receptor (KOR) signaling, a process known to produce aversion and dysphoria in humans and other species. This endogenous opioid system is dysregulated in stress-related disorders, specifically in major depressive disorder (MDD). These findings serve as the foundation for a growing interest in the therapeutic potential of KOR antagonists as novel antidepressants. In this review, data supporting the hypothesis of dysregulated KOR function in MDD are considered. The clinical data demonstrating the therapeutic efficacy and safety of selective and mixed opioid antagonists are then presented. Finally, the preclinical evidence illustrating the induction of behaviors relevant to the endophenotypes of MDD and KOR antagonist activity in stress-naïve and stress-exposed animals is evaluated. Overall, this review highlights the emergent literature supporting the pursuit of KOR antagonists as novel therapeutics for MDD and other stress-related disorders.
Peri-Operative Chemotherapy or Surveillance in Upper Tract Urothelial Cancer (POUT - CRUK/11/027) - A New Randomised Controlled Trial to Define Standard Post-Operative Management
Authors: A.J. Birtle, R. Lewis, J. Chester, J. Donovan, M. Johnson, R.J. Jones, R. Kockelbergh, T.B. Powles, E. Jones, E. Hall
Journal: Annals of Oncology (2012)
Respiratory muscle ultrasonography: methodology, basic and advanced principles and clinical applications in ICU and ED patients—a narrative review
Authors: Pieter R. Tuinman, Annemijn H. Jonkman, Martin Dres, Zhong-Hua Shi, Ewan C. Goligher, Alberto Goffi, Chris de Korte, Alexandre Demoule, Leo Heunks
Journal: Intensive Care Medicine (2020)

Respiratory muscle ultrasound is used to evaluate the anatomy and function of the respiratory muscle pump. It is a safe, repeatable, accurate, and non-invasive bedside technique that can be successfully applied in different settings, including general intensive care and the emergency department. Mastery of this technique allows the intensivist to rapidly diagnose and assess respiratory muscle dysfunction in critically ill patients and in patients with unexplained dyspnea. Furthermore, it can be used to assess patient–ventilator interaction and weaning failure in critically ill patients. This paper provides an overview of the basic and advanced principles underlying respiratory muscle ultrasound with an emphasis on the diaphragm. We review different ultrasound techniques useful for monitoring of the respiratory muscle pump and possible therapeutic consequences. Ideally, respiratory muscle ultrasound is used in conjunction with other components of critical care ultrasound to obtain a comprehensive evaluation of the critically ill patient. We propose the ABCDE-ultrasound approach, a systematic ultrasound evaluation of the heart, lungs and respiratory muscle pump, in patients with weaning failure.
Carboplatin and Pemetrexed Followed by Pemetrexed for Elderly Advanced Non-Small Cell Lung Cancer Patients without Chemotherapy, Multi-Center, Phase I/II Trial
Authors: A. Tamiya, M. Tamiya, M. Kandu, K. Asami, K. Okishio, T. Kawaguchi, S. Atagi, H. Suzuki, N. Okamoto, S. Kobayashi, N. Shiroyama, N. Morishita, T. Tsuji, A. Hirooka, T. Hirashima
Journal: Annals of Oncology (2012)
Pain Interference Outcomes in a Randomized Phase 3 Clinical Trial of Denosumab vs Zoledronic Acid (ZA) in Patients with Solid Tumors and Bone Metastases
Authors: C. Cleeland, L. Fallowfield, R. von Moos, D. Patrick, D.H. Henry, V. Hirsh, K. Zarogoulidis, A. Feng, Z. Cong, A. Braun
Journal: Annals of Oncology (2012)
First Physical, Reprised
Authors: Rita F. Redberg, Mitchell H. Katz
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Recist Response of the Primary Lesion in Metastatic Renal Cell Carcinomas Treated with Sunitinib: Does the Primary Lesion have to be regarded as a Target Lesion?
Authors: I. Park, K. Park, S. Park, Y. Ahn, J. Ahn, H.J. Choi, C. Song, H. Ahn, J.H. Hong, J. Lee
Journal: Annals of Oncology (2012)
P-0301 Circulating Folate, Vitamine B12, Homocysteine, and Risk of Colorectal Cancer: A Case-Control Study in Tunisian Population
Authors: Landolsi Sondess, Kassab Asma, Gharbi Olfa, Chabchoub Imene, Ezzairri Faten, Hochlef Makram, Leila Ben Fatma, Abdelhedi Miled, Ahmed Slim Ben
Journal: Annals of Oncology (2012)
Impact of respiratory muscle training on respiratory muscle strength, respiratory function and quality of life in individuals with tetraplegia: a randomised clinical trial
Authors: Claire L Boswell-Ruys, Chaminda R H Lewis, Nirupama S Wijeysuriya, Rachel A McBain, Bonsan Bonne Lee, David K McKenzie, Simon C Gandevia, Jane E Butler
Journal: Thorax (2020)

Background Respiratory complications remain a leading cause of morbidity and mortality in people with acute and chronic tetraplegia. Respiratory muscle weakness following spinal cord injury-induced tetraplegia impairs lung function and the ability to cough. In particular, inspiratory muscle strength has been identified as the best predictor of the likelihood of developing pneumonia in individuals with tetraplegia. We hypothesised that 6 weeks of progressive respiratory muscle training (RMT) increases respiratory muscle strength with improvements in lung function, quality of life and respiratory health. Methods Sixty-two adults with tetraplegia participated in a double-blind randomised controlled trial. Active or sham RMT was performed twice daily for 6 weeks. Inspiratory muscle strength, measured as maximal inspiratory pressure (PImax) was the primary outcome. Secondary outcomes included lung function, quality of life and respiratory health. Between-group comparisons were obtained with linear models adjusting for baseline values of the outcomes. Results After 6 weeks, there was a greater improvement in PImax in the active group than in the sham group (mean difference 11.5 cmH 2 O (95% CI 5.6 to 17.4), p&lt;0.001) and respiratory symptoms were reduced (St George Respiratory Questionnaire mean difference 10.3 points (0.01–20.65), p=0.046). Significant improvements were observed in quality of life (EuroQol-Five Dimensional Visual Analogue Scale 14.9 points (1.9–27.9), p=0.023) and perceived breathlessness (Borg score 0.64 (0.11–1.17), p=0.021). There were no significant improvements in other measures of respiratory function (p=0.126–0.979). Conclusions Progressive RMT increases inspiratory muscle strength in people with tetraplegia, by a magnitude which is likely to be clinically significant. Measurement of baseline PImax and provision of RMT to at-risk individuals may reduce respiratory complications after tetraplegia. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN 12612000929808).
Quality of Life in Flags Trial a Randomized, Comparative, Open Label, Multicenter, Phase 3 of S-1 + Cisplatin (CS) Compared to 5-Fu + Cisplatin (CF) in Untreated advanced Gastric Cancer (AGC) Patients
Authors: G. Bodoky, A. Carrato, A. Ravaioli, J.A. Ajani
Journal: Annals of Oncology (2012)
Switching to systemic therapy after locoregional treatment failure: Definition and best timing
Authors: Sadahisa Ogasawara, Yoshihiko Ooka, Keisuke Koroki, Susumu Maruta, Hiroaki Kanzaki, Kengo Kanayama, Kazufumi Kobayashi, Soichiro Kiyono, Masato Nakamura, Naoya Kanogawa, Tomoko Saito, Takayuki Kondo, Eiichiro Suzuki, Shingo Nakamoto, Akinobu Tawada, Tetsuhiro Chiba, Makoto Arai, Jun Kato, Naoya Kato
Journal: Clinical and Molecular Hepatology (2020)

In patients with unresectable hepatocellular carcinoma (HCC) without both macrovascular invasion and extrahepatic metastasis, the initial treatment choice recommended is transarterial chemoembolization (TACE). Before sorafenib came into wide use, TACE had been pointlessly carried out repeatedly. It was in the early 2010s that the concept of TACE refractory was advocated. Two retrospective studies from Japan indicated that conversion from TACE to sorafenib the day after patients were deemed as TACE refractory improved overall survival compared with continued TACE, according to the definition by the Japan Society of Hepatology. Nowadays, phase 3 trials have shown clinical benefits of several novel molecular target agents. Compared with the era of sorafenib, sequential treatments with these molecular target agents have gradually prolonged patients’ survival and have become major strategies in patients with HCC. Taking these together, conversion from TACE to systemic therapies at the time of TACE refractory, compared with before, may have a greater impact on survival and may be considered deeper in the decisions-making process in patients with unresectable HCC who are candidate for TACE. Up-to-date information on the concept of TACE refractory is summarized in this review. We believe that the survival of patients with unresectable HCC without both macrovascular invasion and extrahepatic metastasis may be dramatically improved by optimal timing of TACE refractory and switching to systemic therapies.
Severe Cardiotoxicity in a Patient with Renal Cell Carcinoma Treated with MTOR Inhibitor: A case Report
Authors: W. Shioyama, M. Mukai, E. Tone, H. Harada, N. Awata, M. Hori, Y. Arai, K. Nishimura, T. Yamazaki
Journal: Annals of Oncology (2012)
LRRTM4: A Novel Regulator of Presynaptic Inhibition and Ribbon Synapse Arrangements of Retinal Bipolar Cells
Authors: Raunak Sinha, Tabrez J. Siddiqui, Nirmala Padmanabhan, Julie Wallin, Chi Zhang, Benyamin Karimi, Fred Rieke, Ann Marie Craig, Rachel O. Wong, Mrinalini Hoon
Journal: Neuron (2020)
A Prognostic Index for Acute and Lymphoma Type Adult T-Cell Leukemia/Lymphoma
Authors: T. Yamanaka, H. Katsuya, K. Ishitsuka, A. Utsunomiya, H. Sasaki, S. Hanada, T. Eto, Y. Moriuchi, Y. Saburi, M. Miyahara, E. Sueoka, N. Uike, S. Yoshida, J. Suzumiya, K. Tamura
Journal: Annals of Oncology (2012)
Infectiousness of patients with smear-negative pulmonary tuberculosis, assessed by Real-time Polymerase Chain Reaction, XpertⓇMTB/RIF
Authors: Daniel Camprubí, Aina Gomila, Maria D. Grijota-Camino, Laura Soldevila, Maria J. Luque, Fernando Alcaide, Jordi Dorca, Miguel Santin
Journal: Journal of Infection (2020)
Comparisons between non-alcoholic steatohepatitis and alcohol-related hepatocellular carcinoma
Authors: Rahul Kumar, Boon-Bee George Goh, Jia-Wen Kam, Pik-Eu Chang, Chee-Kiat Tan
Journal: Clinical and Molecular Hepatology (2020)

Background/Aims: Non-alcoholic liver disease and alcoholic liver disease begin as simple steatosis that may progress to steatohepatitis and ensuing liver-related complications such as cirrhosis and hepatocellular carcinoma (HCC). We explored differences in characteristics between non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis-related (ASH) HCC.Methods: NASH and ASH patients were identified from our department’s prospective HCC database. A total of 54 and 45 patients met predefined inclusion and exclusion criteria for the NASH-HCC and ASH-HCC groups, respectively. Clinical, biochemical and tumor characteristics were studied.Results: NASH-HCC patients were older compared to ASH-HCC patients (72±9 vs. 66±9 years, &lt;i&gt;P&lt;/i&gt;&lt;0.001) and less male predominant (65% vs. 98%, &lt;i&gt;P&lt;/i&gt;&lt;0.001). Prevalence of diabetes mellitus (78% vs. 36%, &lt;i&gt;P&lt;/i&gt;&lt;0.001) and hypertension (80% vs. 58%, &lt;i&gt;P&lt;/i&gt;&lt;0.001) were significantly higher in the NASH-HCC group. Liver function tests and Child-Pugh scores were similar. There were no differences in alpha-fetoprotein level, lesions found at diagnosis (unifocal/multifocal) or prevalence of portal vein invasion. In both groups, almost half of the patients were in TNM stage 4 at the time of diagnosis and more than 50% of patients were not suitable for any therapy. Median survival in the NASH-HCC and ASH-HCC groups were 13 and 7 months respectively (&lt;i&gt;P&lt;/i&gt;=0.113).Conclusions: Despite significant differences in demography of the NASH-HCC and ASH-HCC groups, liver and tumor characteristics were comparable. Most patients were diagnosed late and were not amenable to curative or locoregional therapies. Better characterization of patients with NASH and ASH at risk of HCC is necessary to optimize screening, surveillance, and management strategies.
Quantitative metastatic lymph node burden and survival in Merkel cell carcinoma
Authors: Anthony T. Nguyen, Michael Luu, Diana J. Lu, Omid Hamid, Jon Mallen-St. Clair, Mark B. Faries, Nima M. Gharavi, Allen S. Ho, Zachary S. Zumsteg
Journal: Journal of the American Academy of Dermatology (2020)