tbuckley/cabot-search huggingface dataset:
Effect of the serine proteases inhibitor gabexate mesylate (GM) on the activity of gemcitabine (G) in cell lines of pancreatic cancer (PC)
Authors: G. Brandi, P. Paterini, S. Tavolari, G. Da Pozzo, E. Nobili, R. Di Cicilia, M. Di Marco, M. Pantaleo, F. De Rosa, G. Biasco
Journal: Journal of Clinical Oncology (2009)

e15645 Background: Negligible advances for PC treatment have been done over the last decade and G remains the standard. Proteolitic degradation of extracellular matrix (ECM) is essential for early local invasion, metastasis and desmoplastic reaction characterizing PC. Differently from MMPs, the serine proteases (uPA and TAT) action is earlier and larger, degradating not only ECM, but also basement membrane, and activating trypsin, plasmin, angiogenesis via TGF-β1 and proliferation via PAR-2. GM is an inhibitor of u-PA,TAT, trypsin and plasmin, used in Italy and Japan for prophylaxis of acute pancreatitis after ERCP. In a previous study, GM demonstrated antinvasion and antimetastatic activity. Study aim: to evaluate if GM increases G efficacy on pancreatic cancer cell line. Methods: In vitro study of phenotypic effects of GM and G in poor differentiated PANC-1 PC cell line using:1) Cell vitality test (Trypan blu);2) Invasion test (Matrigel invasion assay);3) Cell cycle analysis (cytofluorimeter);4) Antiangiogenic test (tube formation assay in extracellular matrix using E.A.hy926 endothelial cells with matrigel). Different doses of G and GM (100,200,250,500 μM;1mM) alone or combined (concomitant or sequential) have been tested vs controls (PANC-1 without any treatment). All tests have been done in triplicate. Results: G alone (250 μM) decreases invasion by 40% (±5,6%) and cell vitality by 15% (±1,3%.). GM alone (100 μM) decreases invasion by 30% (±4,6%.) but 1mM is needed for similar vitality decrease. GM+G together are detrimental vs G alone while sequential treatment (GM before G with or without 24 hours of interval) enhances G activity. GM (200 μM) and G (250 μM) in immediate sequence show better results decreasing ability of invasion by 75% (±8,3%). Cell vitality is better inhibited from GM (100)/G (250) 24 h-delayed sequence by 28% (±3,8%). Combined treatment mainly blocks cells in G1 phase of cell cycle (5%±0,5%) vs controls. Concerning antiangiogenic assay, the administration of G alone is ineffective to inhibit angiogenesis, while pre-treatment with GM results in a strong anti-angiogenic effect. Conclusions: Association of GM to G could represent a new effective approach to inhibit invasion, angiogenesis and growth in pancreatic cancer. No significant financial relationships to disclose.
Phase 2 study of nilotinib in pediatric patients with Philadelphia chromosome–positive chronic myeloid leukemia
Authors: Nobuko Hijiya, Alexey Maschan, Carmelo Rizzari, Hiroyuki Shimada, Carlo Dufour, Hiroaki Goto, Hyoung Jin Kang, Terri Guinipero, Zeynep Karakas, Francisco Bautista, Stéphane Ducassou, Keon Hee Yoo, Christian Michel Zwaan, Frédéric Millot, Paola Aimone, Alex Allepuz, Sara Quenet, Florence Hourcade-Potelleret, Sabine Hertle, Darintr Sosothikul
Journal: Blood (2019)
Cardiovascular Corner
Authors: Jennifer Abbasi
Journal: JAMA (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 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
Increased mortality in patients with corticosteroid-dependent asthma: a nationwide population-based study
Authors: Hyun Lee, Jiin Ryu, Eunwoo Nam, Sung Jun Chung, Yoomi Yeo, Dong Won Park, Tai Sun Park, Ji-Yong Moon, Tae-Hyung Kim, Jang Won Sohn, Ho Joo Yoon, Sang-Heon Kim
Journal: European Respiratory Journal (2019)

Chronic systemic corticosteroid (CS) therapy is associated with an increased risk of mortality in patients with many chronic diseases. However, it has not been elucidated whether chronic systemic CS therapy is associated with increased mortality in patients with asthma. The aim of this study was to determine the effects of chronic systemic CS therapy on long-term mortality in adult patients with asthma.A population-based matched cohort study of males and females aged ≥18 years with asthma was performed using the Korean National Health Insurance Service database from 2005 to 2015. Hazard ratio (HR) with 95% confidence interval for all-cause mortality among patients in the CS-dependent cohort (CS use ≥6 months during baseline period) relative to those in the CS-independent cohort (CS use <6 months during baseline period) was evaluated.The baseline cohort included 466 941 patients with asthma, of whom 8334 were CS-dependent and 458 607 were CS-independent. After 1:1 matching, 8334 subjects with CS-independent asthma were identified. The HR of mortality associated with CS-dependent asthma relative to CS-independent asthma was 2.17 (95% CI 2.04-2.31). In patients receiving low-dose CS, the HR was 1.84 (95% CI 1.69-2.00); in patients receiving high-dose CS, the HR was 2.56 (95% CI 2.35-2.80).In this real-world, clinical practice, observational study, chronic use of systemic CS was associated with increased risk of mortality in patients with asthma, with a significant dose-response relationship between systemic CS use and long-term mortality.
Successful MPB Therapy Followed By Bortezomib Maintenance for Non-Transplant Eligible Patients with Newly Diagnosed Multiple Myeloma: Japanese Phase 2 Study - Broad-J Study
Authors: Michihide Tokuhira, Naoki Takezako, Yoichi Imai, Tadao Ishida, Tomonori Nakazato, Kinuko Mitani, Tohru Ikuta, Morio Matsumoto, Takayuki Ikezoe, Jun Taguchi, Kensuke Usuki, Takeshi Shimomura, Kenkou Chin, Shunya Arai, Kazuma Ohyashiki, Miho Nara, Kenji Kishi, Yoshiaki Kuroda, Yuichi Nakamura, Hisashi Wakita, Makoto Sasaki, Hirotoshi Kamata, Yoshikazu Ichikawa, Akihiko Yokoyama, Kenshi Suzuki, Masahiro Kizaki
Journal: Blood (2017)
“It’s All in Your Head”—Medicine’s Silent Epidemic
Authors: Matthew J. Burke
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
The Potential for Machine Learning–Based Wearables to Improve Socialization in Teenagers and Adults With Autism Spectrum Disorder
Authors: Abhimanyu S. Ahuja
Journal: JAMA Pediatrics (2019)

To the Editor I read the article by Voss et al1 with great interest. With the rise in prevalence of autism spectrum disorder (ASD) in the United States, addressing the ASD-related concern of socialization deficits has become exceedingly important.
Bioavailability of Drugs
Authors: Jan Koch-Weser
Journal: New England Journal of Medicine (1974)

Therapeutic Importance of Bioavailability FactorsMajor variations in the completeness of absorption of a drug are always therapeutically important. Changes in bioavailability are invariably reflected in the concentration of the drug in the circulation and at the site of drug action. The intensity of the therapeutic and toxic actions of many drugs correlates well with their concentration in the serum.23 Even when such correlation is not close or sustained, the amount of drug reaching the site of action inevitably influences the intensity of its effect. The influence of total bioavailability on pharmacologic activity obtains whether the drug is given as . . .
Abstract P032: Feasibility, safety and efficacy of a modified Dietary Approaches to Stop Hypertension diet for Japanese population
Authors: Naoko Miyagawa, Hisatomi Arima, Katsushi Yoshita, Nagako Okuda, Takayoshi Ohkubo, Takashi Hisamatsu, Keiko Kondo, Katsuyuki Miura
Journal: Circulation (2018)

Introduction: The Dietary Approaches to Stop Hypertension (DASH) eating pattern is widely used for lowering blood pressure in the United States. Food preference and intake volume are quite different among American and Japanese diet; therefore, it is necessary to develop a modified version of DASH dietary pattern for Japanese people (JDASH). Hypothesis: The JDASH is feasible, safe and effective among Japanese people. Methods: This crossover pilot study recruited Japanese men and women aged 30 years and over. Participants were randomized to a three week JDASH diet followed by a three week control diet, or the reverse sequence. Intervention periods were separated by two weeks’ washout in which participants returned to their usual diet. The JDASH dietary pattern consisted of higher potassium, magnesium, calcium, dietary fiber, and n-3 fatty acid and lower sodium than Japanese typical diet. The nutrient balance of the control diet was average Japanese diet based on the National Health and Nutrition Survey in Japan. Primary outcome of this trial was a change in 24 hour urine sodium-to-potassium (Na/K) ratios and secondary outcomes were changes in home and office blood pressure values, lipoprotein profiles and body mass index. These outcomes were from 24 hour urine and blood specimens taken measured before and on the last day of each experimental period. The impact on these measurements was calculated with generalized estimating equation model in consideration of the sequences of intervention. Results: The JDASH diet was well tolerated and with no dropouts. No participant reported any adverse effect regarding this intervention diet and no adverse effects were also observed in biological measures. There were no differences in biological measurements between two diets before intervention. A significant difference in 24 hour urine Na/K ratio was observed (-4.33 mol/mol, p&lt;0.001) between the JDASH diet and the control diet. The differences of systolic blood pressure were - 2.1 mmHg (p=0.396) at the office and -0.1 mmHg (p=0.956) at home, respectively. Significant differences in body mass index and low density lipoprotein were -0.4 kg/m 2 (p=0.002) and -11.0 mg/dl (p=0.038), respectively. Conclusion: Developed modified DASH dietary pattern for Japanese were significantly decrease 24 hour urine Na/K ratio. In conclusion, the results of this pilot study showed the feasibility, safety and efficacy.
Targeting the mTOR pathway in idiopathic multicentric Castleman disease
Authors: Robert M. Stern, Nancy Berliner
Journal: Journal of Clinical Investigation (2019)

Idiopathic multicentric Castleman disease (iMCD) is a rare hematologic illness of systemic inflammation and organ dysfunction, with unknown etiology. Although therapies targeting IL-6 have been proven effective, a subset of patients with iMCD are resistant to this approach. In this issue of the JCI, Fajgenbaum et al. performed an in-depth analysis of serum inflammatory markers in three iMCD patients refractory to IL-6 blockade, and identified activation of the mTOR pathway associated with symptom flares. Treatment with sirolimus, an mTOR inhibitor, induced remission in all three patients. This study models a precision medicine approach to discovering therapies for rare diseases.
Intratumoral immunotherapy with TLR7/8 agonist MEDI9197 modulates the tumor microenvironment leading to enhanced activity when combined with other immunotherapies
Authors: Stefanie R. Mullins, John P. Vasilakos, Katharina Deschler, Iwen Grigsby, Pete Gillis, Julius John, Matthew J. Elder, John Swales, Elina Timosenko, Zachary Cooper, Simon J. Dovedi, Andrew J. Leishman, Nadia Luheshi, James Elvecrog, Ashenafi Tilahun, Richard Goodwin, Ronald Herbst, Mark A. Tomai, Robert W. Wilkinson
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Immune checkpoint blockade (ICB) promotes adaptive immunity and tumor regression in some cancer patients. However, in patients with immunologically “cold” tumors, tumor-resident innate immune cell activation may be required to prime an adaptive immune response and so exploit the full potential of ICB. Whilst Toll-like receptor (TLR) agonists have been used topically to successfully treat some superficial skin tumors, systemic TLR agonists have not been well-tolerated. <h3>Methods</h3> The response of human immune cells to TLR7 and 8 agonism was measured in primary human immune cell assays. MEDI9197 (3M-052) was designed as a novel lipophilic TLR7/8 agonist that is retained at the injection site, limiting systemic exposure. Retention of the TLR7/8 agonist at the site of injection was demonstrated using quantitative whole-body autoradiography, HPLC-UV, and MALDI mass spectrometry imaging. Pharmacodynamic changes on T cells from TLR7/8 agonist treated B16-OVA tumors was assessed by histology, quantitative real time PCR, and flow cytometry. Combination activity of TLR7/8 agonism with immunotherapies was assessed in vitro by human DC-T cell MLR assay, and in vivo using multiple syngeneic mouse tumor models. <h3>Results</h3> Targeting both TLR7 and 8 triggers an innate and adaptive immune response in primary human immune cells, exemplified by secretion of IFNα, IL-12 and IFNγ. In contrast, a STING or a TLR9 agonist primarily induces release of IFNα. We demonstrate that the TLR7/8 agonist, MEDI9197, is retained at the sight of injection with limited systemic exposure. This localized TLR7/8 agonism leads to Th1 polarization, enrichment and activation of natural killer (NK) and CD8<sup>+</sup> T cells, and inhibition of tumor growth in multiple syngeneic models. The anti-tumor activity of this TLR7/8 agonist is enhanced when combined with T cell-targeted immunotherapies in pre-clinical models. <h3>Conclusion</h3> Localized TLR7/8 agonism can enhance recruitment and activation of immune cells in tumors and polarize anti-tumor immunity towards a Th1 response. Moreover, we demonstrate that the anti-tumor effects of this TLR7/8 agonist can be enhanced through combination with checkpoint inhibitors and co-stimulatory agonists.
A Dual‐Model Imaging Theragnostic System Based on Mesoporous Silica Nanoparticles for Enhanced Cancer Phototherapy
Authors: Chenlu Huang, Zhiming Zhang, Qing Guo, Li Zhang, Fan Fan, Yu Qin, Hai Wang, Sheng Zhou, Wenbin Ou‐Yang, Hongfan Sun, Xigang Leng, Xiangbin Pan, Deling Kong, Linhua Zhang, Dunwan Zhu
Journal: Advanced Healthcare Materials (2019)

Abstract Mesoporous silica nanoparticles (MSNs) show great promise to be exploited as versatile multifunctional nanocarriers for effective cancer diagnosis and treatment. In this work, perfluorohexane (PFH)‐encapsulated MSNs with indocyanine green (ICG)–polydopamine (PDA) layer and poly(ethylene glycol)–folic acid coating (designated as MSNs‐PFH@PDA‐ICG‐PEG‐FA) are successfully fabricated to achieve tumor ultrasonic (US)/near‐infrared fluorescence (NIRF) imaging as well as photothermal therapy (PTT)/photodynamic therapy (PDT). MSNs‐PFH@PDA‐ICG‐PEG‐FA exhibits good monodispersity with high ICG loading, significantly enhances ICG photostability, and greatly improves cellular uptake. Upon single 808 nm NIR irradiation, the nanocarrier not only efficiently generates hyperthermia to realize PTT, but also produces reactive oxygen species (ROS) for effective PDT. Meanwhile, NIR irradiation can trigger PFH to undergo vaporization and provide a super‐resolution US image. Thus, the PTT/PDT combination therapy can be dually guided by PFH‐induced US imaging and ICG‐induced NIRF imaging. In vivo antitumor studies demonstrate that PTT/PDT from MSNs‐PFH@PDA‐ICG‐PEG‐FA significantly inhibits tumor growth and achieves a cure rate of 60% (three out of five mice are completely cured). Hence, the multifunctional MSNs appear to be a promising theragnostic nanoplatform for multimodal cancer imaging and therapy.
Germinal center T <sub>FH</sub> cells: T(w)o be or not t(w)o be, IL-6 is the answer
Authors: Pengcheng Zhou, Kaili Liang, Di Yu
Journal: Science Immunology (2019)

IL-6 inhibits the expression of IL-2Rβ (CD122) in germinal center T FH cells to maintain IL-2 hyporesponsiveness (see the related Research Article by Papillion et al . ).
Distinguishing blood and lymph vessel invasion in breast cancer: a prospective study in 95 patients.
Authors: Gert G. Van Den Eynden, Ilse Van der Auwera, Steven L. Van Laere, Cecile C. Colpaert, Peter Van Dam, Peter B. Vermeulen, Luc Y. Dirix, Eric A. Van Marck
Journal: Cancer Research (2006)

5169  Introduction. Blood (BVI) and lymph vessel invasion (LVI) are the histological correlates of the first steps of haematogenous and lymphatic metastasis in solid tumors. Historically it has been difficult to study both processes, especially histomorphologically, due to lack of specific markers. The discovery and characterization of new lymphatic endothelium markers such as D2-40, make it now possible to distinghuish between blood and lymph vessels . Therefore, the aim of this prospective study was to quantify and compare BVI and LVI in a consecutive series of breast cancer patients. Materials and Methods. Three consecutive 5 μm sections of all FFPE tissue blocks of the resection specimen of 95 consecutive patients with operable breast cancer were (immuno)histochemically stained in a fixed order: HE, anti-CD34 (pan-endothelium) and anti-D2-40 (lymphatic endothelium) antibodies. On every slide, all vessels with vascular invasion were marked and relocated on the corresponding slides. Based on the IHC staining pattern, vascular invasion was assessed as being LVI (CD34+or−/D2-40+) or BVI (CD34+/D2-40-). LVI and BVI were assessed as intra- (in contact with tumor cells or desmoplastic stroma) or peritumoral. The number of intra- and peritumoral vessels with LVI and BVI per patient was counted as well as the number of tumor cells in every vessel. Results were correlated with clinico-pathological variables, the growth pattern and the presence of a fibrotic focus. Results. In total 3297 (661 intra, 2636 peri) vessels with LVI and 135 (80 intra, 63 peri) vessels with BVI were seen. The median number of FFPE blocks per patient was 4. 66 (69.5%) patients had LVI (8 intratumoral, 35 peritumoral, 23 intra- and peritumoral), compared to 36 (37.9%) patients with BVI (12 intra-, 8 peri- and 16 intra- and peritumoral). Although LVI and BVI were associated intratumorally (p=0.02), only LVI, not BVI correlated with the presence of LN metastases (p intra=0.07, p peri=0.002).T2 tumors more often showed LVI (p
Final analysis from RESONATE: Up to six years of follow‐up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma
Authors: Talha Munir, Jennifer R. Brown, Susan O'Brien, Jacqueline C. Barrientos, Paul M. Barr, Nishitha M. Reddy, Steven Coutre, Constantine S. Tam, Stephen P. Mulligan, Ulrich Jaeger, Thomas J. Kipps, Carol Moreno, Marco Montillo, Jan A. Burger, John C. Byrd, Peter Hillmen, Sandra Dai, Anita Szoke, James P. Dean, Jennifer A. Woyach
Journal: American Journal of Hematology (2019)

Abstract Ibrutinib, a once‐daily oral inhibitor of Bruton's tyrosine kinase, is approved in the United States and Europe for treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The phase 3 RESONATE study showed improved efficacy of single‐agent ibrutinib over ofatumumab in patients with relapsed/refractory CLL/SLL, including those with high‐risk features. Here we report the final analysis from RESONATE with median follow‐up on study of 65.3 months (range, 0.3‐71.6) in the ibrutinib arm. Median progression‐free survival (PFS) remained significantly longer for patients randomized to ibrutinib vs ofatumumab (44.1 vs 8.1 months; hazard ratio [HR]: 0.148; 95% confidence interval [CI]: 0.113‐0.196; P ˂.001). The PFS benefit with ibrutinib vs ofatumumab was preserved in the genomic high‐risk population with del(17p), TP53 mutation, del(11q), and/or unmutated IGHV status (median PFS 44.1 vs 8.0 months; HR: 0.110; 95% CI: 0.080‐0.152), which represented 82% of patients. Overall response rate with ibrutinib was 91% (complete response/complete response with incomplete bone marrow recovery, 11%). Overall survival, censored for crossover, was better with ibrutinib than ofatumumab (HR: 0.639; 95% CI: 0.418‐0.975). With up to 71 months (median 41 months) of ibrutinib therapy, the safety profile remained consistent with prior reports; cumulatively, all‐grade (grade ≥3) hypertension and atrial fibrillation occurred in 21% (9%) and 12% (6%) of patients, respectively. Only 16% discontinued ibrutinib because of adverse events (AEs). These long‐term results confirm the robust efficacy of ibrutinib in relapsed/refractory CLL/SLL irrespective of high‐risk clinical or genomic features, with no unexpected AEs. This trial is registered at www.clinicaltrials.gov (NCT01578707).
Reproducible biomedical benchmarking in the cloud: lessons from crowd-sourced data challenges
Authors: Kyle Ellrott, Alex Buchanan, Allison Creason, Michael Mason, Thomas Schaffter, Bruce Hoff, James Eddy, John M. Chilton, Thomas Yu, Joshua M. Stuart, Julio Saez-Rodriguez, Gustavo Stolovitzky, Paul C. Boutros, Justin Guinney
Journal: Genome biology (2019)

Challenges are achieving broad acceptance for addressing many biomedical questions and enabling tool assessment. But ensuring that the methods evaluated are reproducible and reusable is complicated by the diversity of software architectures, input and output file formats, and computing environments. To mitigate these problems, some challenges have leveraged new virtualization and compute methods, requiring participants to submit cloud-ready software packages. We review recent data challenges with innovative approaches to model reproducibility and data sharing, and outline key lessons for improving quantitative biomedical data analysis through crowd-sourced benchmarking challenges.