tbuckley/cabot-search huggingface dataset:
An investigation of the safety of continued treatment with sorafenib in patients with unresectable hepatocellular carcinoma after the first disease progression: Multicenter, open-label, phase II safety study.
Authors: Noriyuki Akutsu, Shigeru Sasaki, Hideyasu Takagi, Hiroyuki Kaneto, Kazuhiko Yonezawa, Atsushi Yawata, Takeya Adachi, Hideki Yokoo, Toshiya Kamiyama, Yasuo Hamamoto, Yasuhisa Shinomura
Journal: Journal of Clinical Oncology (2015)

462 Background: Randomized studies showed that sorafenib significantly improved outcome in patients with unresectable hepatocellular carcinoma (HCC). However, there is no clear evidence to support the safety and benefit of continued treatment of sorafenib beyond disease progression (PD) in patients with HCC treated with sorafenib. We prospectively evaluated the safety and efficacy of sorafenib beyond PD in patients with HCC whose disease has progressed after first-line treatment with sorafenib. Methods: Unresectable HCC patients with evaluable lesion were treated with sorafenib until 1st PD, followed by soafenib until 2nd PD. The primary endpoint of the study was the safety after 1st PD until 2nd PD. Secondary endpoints of the study were response rate (RR), disease control rate (DCR), time to first PD (TTP1), time to second PD during continued treatment (TTP2), overall survival (OS), and safety throughout the treatment period. Adverse event was evaluated as per The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated as per Modified Response Evaluation in Solid Tumors (mRECIST) criteria. The Kaplan–Meier method was used to determine TTP and OS. Results: Of 30 patients enrolled from 6 sites in Japan, 29 patients received sorafenib treatment, and one patient refused chemotherapy. Twenty patients continued sorafenib beyond PD. Grade 3/4 adverse events occurred less frequently during TTP2 than during TTP1. No critical events related to sorafenib were reported during TTP2. In the first-line therapy, 29 patients treated with sorafenib showed RR of 10.3%, DCR of 60.7% and median TTP1 of 102 days. Twenty patients who received continued sorafenib beyond PD and showed RR of 0%, DCR of 45%, and median TTP2 of 77 days. Median survival time was 306 days. Conclusions: Sorafenib beyond PD had acceptable tolerability and considerable efficacy. In the present conditions without second line treatment, sorafenib beyond PD might be one of the treatment options. Clinical trial information: UMIN000005818.
Integrated prevention of mother-to-child HIV transmission services, antiretroviral therapy initiation, and maternal and infant retention in care in rural north-central Nigeria: a cluster-randomised controlled trial
Authors: Muktar H Aliyu, Meridith Blevins, Carolyn M Audet, Marcia Kalish, Usman I Gebi, Obinna Onwujekwe, Mary Lou Lindegren, Bryan E Shepherd, C William Wester, Sten H Vermund
Journal: The Lancet HIV (2016)
The role of methylation leading to capecitabine resistant malignant mesothelioma
Authors: K. V. Kosuri, X. Wu, G. Otterson
Journal: Journal of Clinical Oncology (2006)

17105 Background: Malignant mesothelioma is a deadly malignancy whose global incidence continues to be on the rise. Established therapies have been less than optimal. The current therapeutic standard is intravenous pemetrexed, an antifolate medication. Yet, another folate antimetabolite, capecitabine, is significantly less effective than pemetrexed. The enzymes thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidylate phosphatase (TP) are critical to the efficacy of antifolates. Specifically, for capecitabine to be converted into a potent cytotoxic agent, the enzyme TP must be present and active. In one of four mesothelioma cell lines examined, the gene that encodes for TP, extracellular growth factor-1 (ECGF-1), is methylated. Methylation of this gene and the subsequent downregualtion of the TP enzyme confer a diminished cytotoxic effect by a capecitabine prodrug, dioxyfluridine (DFUR). Methods: Cells were cultured treated with and without 1uM decitabine (DAC) under identical conditions. DNA, RNA, and protein lysates were collected after 72 hours. Bisulfite-treated DNA was examined by MS-PCR for evidence of methylation of TS, DPD, and TP. RNA was collected and cDNA was synthesized. Real time PCR was utilized to detect the relative difference in RNA quantity. Western blots were done to evaluate the differences in protein expression between DAC treated and untreated cells. MTT assay was performed with DAC pretreated and untreated cell lines subsequently treated with DFUR and 5-fluorouracil. Results: One of the four mesothelioma cell lines showed consistent evidence of TP methylation by MS-PCR. The addition of 1uM DAC to the cell lines conferred a six-fold difference in expression of the methylated gene by both real time PCR as well as by Western blot. The prodrug DFUR subsequently shows increased cytotoxicity in the methylated cell line by MTT assay when pretreated with DAC compared when not exposed to the DAC. Conclusion: By demethylating the ECGF-1 gene with DAC, the now upregulated TP enzyme has an increased ability to convert DFUR to 5-FU; thus enhancing the cytotoxicity of a drug thought to be ineffective in malignant mesothelioma. No significant financial relationships to disclose.
Intraoperative radiotherapy (IORT) with low-energy x-rays for breast cancer
Authors: U. S. Kraus-Tiefenbacher, C. Herskind, L. Bauer, A. Scheda, F. Wenz
Journal: Journal of Clinical Oncology (2007)

607 Background: IORT for breast cancer using either electrons or low-energy x-rays is of increasing interest over the last few years. In our institution, IORT is delivered by a mobile x-ray source (Intrabeam™) producing isotropic 50 kV x-ray fields. Because this treatment method includes single high doses to the normal breast tissue, careful and long-term evaluation of early and late toxicity is mandatory. To date there are still fewdata on long-term follow-up of patients treated with low-energy x-rays. Methods: Between 2/02 and 12/06 204 breast cancer patients received IORT either as a tumour-bed boost (133) followed by 46 Gy external beam radiotherapy (EBRT) or as partial breast irradiation (PBI) only (71). Median age was 66.4 years (35–95), median tumour size was 9 mm (1–45). Spherical applicators (median 4. 0 cm) were inserted into the tumour-cavity and a single dose of 20 Gy was given. Follow-up (f/u) included physical examination and ultrasound 1 week, 2 months, then every 6 months after therapy and mammography at yearly intervals. Radiobiological modelling of the expected spatial distribution of late reactions was done for typical cases using the linear-quadratic model with special consideration of relative biological effectiveness, spatial dose distribution and dose rate. Results: Median f/u was 28 months (1–56). Minor postoperative side effects included erythema (5%), delayed wound healing (4%), mastitis (1%) and hematoseroma (4%). A fibrotic induration of the tumour bed was observed in 9, 18, 24, 23, 26% and 24% of the patients at 2, 6 12, 24, 36 and 48 month f/u. These fibrosis rates were distributed equally in both groups. Reoperation was required in 2 patients after 10 (fibrosis) and 12 months (fat necrosis). Conclusions: Although two thirds of the patients were treated with a combination of IORT and EBRT, acute reactions in all patients were mild. A fibrotic induration confined to the tumourbed was observed in up to 25% of all patients after 2 years. The low level of clinically observed late reactions so far is in agreement with predictions from radiobiological modelling. No significant financial relationships to disclose.
Perioperative Statins in Cardiac Surgery and Acute Kidney Injury
Authors: Rinaldo Bellomo
Journal: JAMA (2016)

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
Therapeutic Guide for mTOuRing through the Braided Kidney Cancer Genomic River
Authors: Martin H. Voss, James J. Hsieh
Journal: Clinical Cancer Research (2016)

mTORC1 inhibitors were first approved for the use in metastatic kidney cancer. However, observed treatment benefit was highly heterogeneous among patients. Through case-based cancer genomic sequencing of therapeutic outliers, we can begin to appreciate the convergent evolution of given cancer pathways/phenotypes beyond genes in kidney cancer, like a braided river. Clin Cancer Res; 22(10); 2320-2. ©2016 AACRSee related article by Kwiatkowski et al., p. 2445.
A Phase I Study of Quizartinib Combined with Chemotherapy in Relapsed Childhood Leukemia: A Therapeutic Advances in Childhood Leukemia &amp; Lymphoma (TACL) Study
Authors: Todd M. Cooper, Jeannette Cassar, Elena Eckroth, Jemily Malvar, Richard Sposto, Paul Gaynon, Bill H. Chang, Lia Gore, Keith August, Jessica A. Pollard, Steven G. DuBois, Lewis B. Silverman, Javier Oesterheld, Guy Gammon, Daniel Magoon, Colleen Annesley, Patrick A. Brown
Journal: Clinical Cancer Research (2016)

To determine a safe and biologically active dose of quizartinib (AC220), a potent and selective class III receptor tyrosine kinase (RTK) FLT3 inhibitor, in combination with salvage chemotherapy in children with relapsed acute leukemia.Quizartinib was administered orally to children with relapsed AML or MLL-rearranged ALL following 5 days of high-dose cytarabine and etoposide (AE). A 3+3 dose escalation design was used to identify a safe and biologically active dose. Plasma inhibitory assay (PIA) testing was performed weekly to determine biologic activity.Toxicities were consistent with intensive relapsed leukemia regimens. One of 6 patients experienced a dose-limiting toxicity (DLT) at 40 mg/m(2)/day (elevated lipase) and 1 of 9 had a DLT (hyperbilirubinemia) at the highest tested dose of 60 mg/m(2)/day. Of 17 response evaluable patients, 2 had complete response (CR), 1 complete response without platelet recovery (CRp), 1 complete response with incomplete neutrophil and platelet recovery (CRi), 10 stable disease (SD), and 3 progressive disease (PD). Of 7 FLT3-ITD patients, 1 achieved CR, 1 CRp, 1 Cri, and 4 SD. FLT3-ITD patients, but not FLT3 wild-type (WT) patients, had significantly lower blast counts post-quizartinib. FLT3 phosphorylation was completely inhibited in all patients.Quizartinib plus intensive chemotherapy is well tolerated at 60 mg/m(2)/day with near complete inhibition of FLT3 phosphorylation in all patients. The favorable toxicity profile, pharmacodynamic activity, and encouraging response rates warrant further testing of quizartinib in children with FLT3-ITD AML. Clin Cancer Res; 22(16); 4014-22. ©2016 AACR.
Mouse Monoclonal Antibody to Embryonic Antigen: Development, Cross-Reactivity With Rodent and Human Tumors, and Preliminary Polypeptide Characterization&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: W J Payne, J H Coggin
Journal: JNCI Journal of the National Cancer Institute (1985)

Hybridomas producing IgM and IgG monoclonal antibodies (MoAb) to embryonic or fetal antigens (EA) were obtained in a completely syngeneic system. Lethally irradiated, 13-day-gestation, C57BL/6N mouse fetal cells or KCI extracts of these fetal cells obtained from primaparous donors were used as immunogens in several regimens to induce splenocytes in C57BL/6N mice that were utilized to form the hybridomas following fusion with a mouse myeloma line. Successful growth and cloning of the IgM-producing hybridomas required supplementation with factor(s) produced in the growth medium of the macrophage cell line RAW 264.7. An enzyme-linked immunosorbent assay (ELISA) was employed to screen the primary fusion hybridomas for antibody directed against fetal cell or adult cell determinants with the use of freshly explanted tissues. Glutaraldehyde-fixed fetal cells as well as crude fetal cell membranes were used as EA+ target cells (i.e., cell lines known to activate T-lymphocyte-mediated tumor resistance) in a solid-phase ELISA to perform quantitative ELISA adsorption tests of the MoAb. The anti-EA monoclonal IgM and the IgG detected common, embryo-specific antigen(s) on mouse, hamster, and human fetuses. Term fetal cells and adult normal tissues of the mouse, hamster, and human did not express cross-reactive determinants for the MoAb by absorption analysis and/or by direct binding in ELISA. EA expression as oncofetal antigens could also be detected with the monoclones on several rodent tumor cell lines tested as well as on a variety of human carcinomas but not on a spectrum of normal human tissues with the use of indirect ELISA absorption and affinity gel and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses. Fluorescence analysis with the monoclones demonstrated specific reactivity with the surface of EA+ tumor cells in the FACS IV flow cytometer. The responsible antigen was carried on a 44- and a 200-kilodalton polypeptide.
The impact of three-dimensional imaging on polyp detection during colonoscopy: a proof of concept study
Authors: Shinichiro Sakata, Philip M Grove, Andrew R L Stevenson, David G Hewett
Journal: Gut (2016)

Failures in lesion detection at colonoscopy deliver imperfect protection against colorectal cancer. Minimally elevated lesions are more likely to contain high-grade dysplasia or invasive carcinoma, but are frequently undetected during conventional two-dimensional (2D) colonoscopy. We performed a randomised, complete, across-subjects counterbalanced study of 3D versus 2D imaging for lesion detection during simulated colonoscopy in a simulation laboratory. Thirty-six gastroenterology fellows, comprising 50% of the nationwide pool in Australia, were tested on their ability to detect a 1 mm lesion that was similar in colour and surface texture to its surroundings in 20 simulated colonoscopy withdrawal videos, half of which contained a lesion and the other half were lesion-free. Testing difficulty was maximised to accommodate for ceiling effects, and experimental validity was confirmed by pilot testing using international experts in colonoscopy. We found a 25.1% absolute improvement in detection rates for 3D over 2D imaging. The sensitivity of 3D viewing was approximately twice that of 2D, and the false-positive rates with both technologies were not significantly different. This is the first study to highlight the large and immediate impact of 3D displays in the colonoscopic detection of diminutive, minimally elevated lesions, and the significant potential for the application of 3D technology to colonoscopy.

Minimally elevated or depressed lesions that are more likely to contain high-grade dysplasia or invasive …
Tumor FDG-uptake after the initial cycle of chemotherapy and histopathologic response to neoadjuvant therapy in high-grade soft tissue sarcomas
Authors: M. R. Benz, W. A. Weber, M. S. Allen-Auerbach, W. D. Tap, D. Elashoff, J. J. Eckardt, S. M. Dry, M. E. Phelps, J. Czernin, F. C. Eilber
Journal: Journal of Clinical Oncology (2008)

10528 Background: The ability to identify patients early in the course of treatment who will or will not benefit from treatment is important in patients with high-grade soft tissue sarcomas (STS) due to the toxicity of the chemotherapy and its limited impact on survival. The aim of this study was to prospectively evaluate whether a change in F18-fluorodeoxyglucose uptake measured by positron emission tomography (FDG-PET) after the initial cycle of chemotherapy predicted histopathologic response to neoadjuvant therapy in high-grade STS. Methods: From 2/06 to 8/07 40 patients with resectable high-grade STS scheduled for neoadjuvant therapy were enrolled. Patients underwent a FDG-PET/CT scan prior to neoadjuvant therapy (baseline), after the initial cycle of chemotherapy (early) and at the completion of therapy prior to surgery (follow-up). Tumor FDG uptake was quantified by standardized uptake values (SUV). Following resection, response was assessed histopathologically. Patients with ≥95% pathologic necrosis were classified as responders. Changes in SUV from the baseline to the early scan were compared to histopathologic response. Results: In histopathologic responders (n=8), reduction of tumor FDG uptake after the initial cycle of chemotherapy was significantly more pronounced (−52%) than in histopathologic non-responders (−20%) (p=0.006). All histopathologic responders (8/40=20%) and 13 (13/40=32%) non-responders had a ≥30% reduction in SUV between the baseline and early scan. 19 (19/40=48%) non-responders had a decrease in SUV of <30%. Using a ≥30% reduction in FDG uptake as the threshold value for early metabolic response allowed assessment of histopathologic response with a sensitivity of 100% and a specificity of 59% (p=0.004). Although the positive predictive value was only 38%, the negative predictive value was 100%. Conclusions: A 30% reduction in tumor FDG uptake after the initial cycle of chemotherapy predicted histopathologic response to neoadjuvant therapy in high-grade STS. Although long-term follow-up is needed, the high negative predictive value of FDG-PET suggests that patients who do not achieve this threshold of early metabolic response should proceed to directly to surgery. No significant financial relationships to disclose.
Folate Therapy and In-Stent Restenosis
Authors: Olaf Stanger, Brian Fowler, Wolfgang Herrmann
Journal: New England Journal of Medicine (2004)

1. Keenan SP, Powers C, McCormack DG, Block G. Noninvasive positive-pressure ventilation for postextubation respiratory distress: a randomized controlled trial. JAMA 2002;287:3238-44. 2. Hillberg RE, Johnson DC. Noninvasive ventilation. N Engl J Med 1997;337:1746-52. 3. Mehta S, Hill NS. Noninvasive ventilation. Am J Respir Crit Care Med 2001;163:540-77. 4. International Consensus Conferences in Intensive Care Medicine: noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med 2001;163:283-91.
Lenalidomide (Revlimid), Bortezomib (Velcade) and Dexamethasone (RVD) For The Treatment Of Secondary Plasma Cell Leukaemia
Authors: Victor H Jimenez Zepeda, Donna E. Reece, Suzanne Trudel, Christine I. Chen, Rodger E. Tiedemann, Vishal Kukreti
Journal: Blood (2013)
P70Circulating microRNAs and outcome in patients with acute heart failure
Authors: E Goretti, MF Seronde, M Vausort, E Gayat, T Thum, A Cohen-Solal, DR Wagner, A Mebazaa, Y Devaux
Journal: Cardiovascular Research (2014)

Purpose: Circulating microRNAs (miRNAs) have been extensively studied for their potential biomarker value in patients with acute coronary syndromes. However, the association between miRNAs and the diagnostic and prognostic in patients with acute heart failure (AHF) has received less attention.
Exploring the Potential of Starch/Polycaprolactone Aligned Magnetic Responsive Scaffolds for Tendon Regeneration
Authors: Ana I. Gonçalves, Márcia T. Rodrigues, Pedro P. Carvalho, Manuel Bañobre‐López, Elvira Paz, Paulo Freitas, Manuela E. Gomes
Journal: Advanced Healthcare Materials (2015)

The application of magnetic nanoparticles (MNPs) in tissue engineering (TE) approaches opens several new research possibilities in this field, enabling a new generation of multifunctional constructs for tissue regeneration. This study describes the development of sophisticated magnetic polymer scaffolds with aligned structural features aimed at applications in tendon tissue engineering (TTE). Tissue engineering magnetic scaffolds are prepared by incorporating iron oxide MNPs into a 3D structure of aligned SPCL (starch and polycaprolactone) fibers fabricated by rapid prototyping (RP) technology. The 3D architecture, composition, and magnetic properties are characterized. Furthermore, the effect of an externally applied magnetic field is investigated on the tenogenic differentiation of adipose stem cells (ASCs) cultured onto the developed magnetic scaffolds, demonstrating that ASCs undergo tenogenic differentiation synthesizing a Tenascin C and Collagen type I rich matrix under magneto‐stimulation conditions. Finally, the developed magnetic scaffolds were implanted in an ectopic rat model, evidencing good biocompatibility and integration within the surrounding tissues. Together, these results suggest that the effect of the magnetic aligned scaffolds structure combined with magnetic stimulation has a significant potential to impact the field of tendon tissue engineering toward the development of more efficient regeneration therapies.
Codon usage in the vertebrate hemoglobins and its implications.
Authors: T F Smith, W W Ralph, M Goodman, J Czelusniak
Journal: Molecular Biology and Evolution (1985)

A study of codon usage in vertebrate hemoglobins revealed an evolutionary trend toward elevated numbers of CpG codon boundary pairs in mammalian hemoglobin alpha genes. Selection for CpG codon boundaries countering the generally observed CpG suppression is strongly suggested by these data. These observations parallel recently published experimental results that indicate that constitutive expression of the human alpha-globin gene appears to be determined by regulatory information encoded within the structural gene. The possibility is raised that, in the absence of selection, CpG decay can be used to date the evolutionary origin of a mammalian alpha pseudogene from its active alpha gene.
Liver capsule: Age‐influenced hepatic immune priming determines HBV infection fate: Implications from mouse to man
Authors: Jean Publicover, Jillian M. Jespersen, Audra J. Johnson, Stephen L. Nishimura, Amanda Goodsell, Adil E. Wakil, Philip Rosenthal, Eric Pai, Lia Avanesyan, Stewart Cooper, Jody L. Baron
Journal: Hepatology (2015)

Publicover, Jean; Jespersen, Jillian M.; Johnson, Audra J.; Nishimura, Stephen L.; Goodsell, Amanda; Wakil, Adil E.; Rosenthal, Philip; Pai, Eric; Avanesyan, Lia; Cooper, Stewart; Baron, Jody L. Author Information
Comprehensive quantitative proteomic profiling of the pharmacodynamic changes induced by MLN4924 in acute myeloid leukemia cells establishes rationale for its combination with azacitidine
Authors: V Visconte, S T Nawrocki, C M Espitia, K R Kelly, A Possemato, S A Beausoleil, Y Han, H E Carraway, A Nazha, A S Advani, J P Maciejewski, M A Sekeres, J S Carew
Journal: Leukemia (2015)