tbuckley/cabot-search huggingface dataset:
14-day continuous infusion ifosfamide in advanced refractory sarcomas.
Authors: Arun S. Singh, Kamalesh Kumar Sankhala, Arnob Mukherjee, Vivek Narasimha, Bartosz Chmielowski, Doris V. Quon, Vicky Chua, Sant P. Chawla
Journal: Journal of Clinical Oncology (2014)

10596 Background: Ifosfamide is commonly used to treat bone and soft tissue sarcomas (STS) and its efficacy appears to increase with doses >9g/m2/cycle. Due to the toxicity associated with bolus dosing, 14 day CIV outpatient dosing of this medication is being explored as a less toxic, convenient approach. In this study, we present the results of 51 patients who were treated with this regimen. Methods: 51 Patients with advanced/metastic bone and STS refractory to standard therapies received 1g/m2/day x 14 days of CIV ifosfamide/MESNA; the dosing was adjusted for tolerance/toxicity. 41 patients were from a retrospective cohort and 10 patients are from a prospectively collected study approved by the Western IRB. Grade 3/4 toxicities were recorded. Patients were assessed for objective response via RECIST 1.1. Results: 51 patients received this regimen over the course of 3 years. The most common histologies were high grade leiomyosarcoma (n=18), synovial sarcoma (n=5), HGUPS(n=5), and osteosarcoma (n=5). 63% of patients had 2 or more lines of previous therapy. The response of 6 patients could not be assessed due to death from disease progression, lack of follow up scans or discontinuation of therapy. 1/51 patients had a CR (2%), 11/51 had a PR (23.5%) and the CBR (CR+PR+SD) was 64.5%. The median PFS was 12 weeks (range: 2-120 weeks). Of grade 3/4 hematologic toxicities, 53% had neutropenia, 22% had anemia and 8% had thrombocytopenia. Of grade 3/4 non-hematologic toxicities, 6 patients (11.7%) had confusion, 2 had nausea/vomiting, 1 had CHF and 1 patient died while receiving treatment. No patients had hemorrhagic cystitis. Conclusions: 14 day CIV ifosfamide is a viable option for advanced sarcomas with a CBR of 64.5%. The median PFS of 12 weeks compares favorably to the previously reported data. The data in this study has fostered a prospective evaluation of CIV in advanced sarcomas.
A phase II study of gemcitabine by fixed-dose rate infusion, cisplatin, and celecoxib in metastatic pancreatic cancer
Authors: B. Kobrossy, B. F. El-Rayes, A. F. Shields, U. Vaishampayan, L. Heilbrun, M. M. Zalupski, P. A. Philip
Journal: Journal of Clinical Oncology (2004)

4120 Background: The cyclooxygenase-2 (COX-2) enzyme is overexpressed in 45–72% of pancreatic cancers. Inhibition of the COX-2 sensitises human pancreatic cancer cells to the apoptotic effects of cytotoxic. Gemcitabine by fixed dose rate infusion may improve response rate and survival in patients with pancreas cancer. This phase II study was undertaken to determine the effects of adding celecoxib to a regimen of gemcitabine by fixed dose rate infusion and cisplatin. Methods: The primary endpoint was survival at 6 months in patients with metastatic pancreatic cancer treated with the gemcitabine, cisplatin, and celecoxib regimen. Previously untreated patients with a performance status of 0–2 were eligible for this study. Patients received gemcitabine 1,000 mg/m2 by fixed dose rate (10 mg/m2/min) I.V. infusion, and cisplatin 35 mg/m2 on days 1 and 8 of a 21-day cycle. Celecoxib was administered at a dose 400 mg twice-daily continuously starting day –7 until termination from study. Results: A total of 22 patients (median age 59 years; males 13%) were enrolled on the study. Median performance status was 1. The median number of cycles administered was 2 (range 0–11). Seventeen patients were response evaluable. In intent to treat analysis, objective response and stable disease were seen in 9% (90% CI; 0.02–0.24) and 27%, respectively. Nine patients were alive at 6-months. Median overall survival time was 5.7 months (90% CI; 3.7–7.5 months). No treatment related deaths were observed. The most commonly reported grade 3/4 toxicities were neutropenia (65%), thrombocytopenia (55%), and anemia (35%). The majority of the patients required dose reductions of gemcitabine and cisplatin. Conclusion: Celecoxib can be safely administered in combination with gemcitabine and cisplatin. The regimen of gemcitabine by the fixed dose rate infusion and cisplatin was associated with significant myelosuppression. The addition of celecoxib to a regimen utilizing gemcitabine by fixed dose rate infusion did not appear to have a significant impact on the 6-month survival rate and overall survival. No significant financial relationships to disclose.
Suppression of Lymphocyte Functions by Plasma Exosomes Correlates with Disease Activity in Patients with Head and Neck Cancer
Authors: Sonja Ludwig, Theofanis Floros, Marie-Nicole Theodoraki, Chang-Sook Hong, Edwin K. Jackson, Stephan Lang, Theresa L. Whiteside
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Head and neck cancers (HNCs) often induce profound immunosuppression, which contributes to disease progression and interferes with immune-based therapies. Body fluids of patients with HNC are enriched in exosomes potentially engaged in negative regulation of antitumor immune responses. The presence and content of exosomes derived from plasma of patients with HNC are evaluated for the ability to induce immune dysfunction and influence disease activity. Experimental Design: Exosomes were isolated by size-exclusion chromatography from plasma of 38 patients with HNC and 14 healthy donors. Morphology, size, numbers, and protein and molecular contents of the recovered exosomes were determined. Coculture assays were performed to measure exosome-mediated effects on functions of normal human lymphocyte subsets and natural killer (NK) cells. The results were correlated with disease stage and activity. Results: The presence, quantity, and molecular content of isolated, plasma-derived exosomes discriminated patients with HNC with active disease (AD) from those with no evident disease (NED) after oncologic therapies. Exosomes of patients with AD were significantly more effective than exosomes of patients with NED in inducing apoptosis of CD8+ T cells, suppression of CD4+ T-cell proliferation, and upregulation of regulatory T-cell (Treg) suppressor functions (all at P &amp;lt; 0.05). Exosomes of patients with AD also downregulated NKG2D expression levels in NK cells. Conclusions: Exosomes in plasma of patients with HNC carry immunosuppressive molecules and interfere with functions of immune cells. Exosome-induced immune suppression correlates with disease activity in HNC, suggesting that plasma exosomes could be useful as biomarkers of HNC progression. Clin Cancer Res; 23(16); 4843–54. ©2017 AACR.
Primates, Lice and Bacteria: Speciation and Genome Evolution in the Symbionts of Hominid Lice
Authors: Bret M. Boyd, Julie M. Allen, Nam-Phuong Nguyen, Pranjal Vachaspati, Zachary S. Quicksall, Tandy Warnow, Lawrence Mugisha, Kevin P. Johnson, David L. Reed
Journal: Molecular Biology and Evolution (2017)

Insects with restricted diets rely on symbiotic bacteria to provide essential metabolites missing in their diet. The blood-sucking lice are obligate, host-specific parasites of mammals and are themselves host to symbiotic bacteria. In human lice, these bacterial symbionts supply the lice with B-vitamins. Here, we sequenced the genomes of symbiotic and heritable bacterial of human, chimpanzee, gorilla, and monkey lice and used phylogenomics to investigate their evolutionary relationships. We find that these symbionts have a phylogenetic history reflecting the louse phylogeny, a finding contrary to previous reports of symbiont replacement. Examination of the highly reduced symbiont genomes (0.53–0.57 Mb) reveals much of the genomes are dedicated to vitamin synthesis. This is unchanged in the smallest symbiont genome and one that appears to have been reorganized. Specifically, symbionts from human lice, chimpanzee lice, and gorilla lice carry a small plasmid that encodes synthesis of vitamin B5, a vitamin critical to the bacteria-louse symbiosis. This plasmid is absent in an old world monkey louse symbiont, where this pathway is on its primary chromosome. This suggests the unique genomic configuration brought about by the plasmid is not essential for symbiosis, but once obtained, it has persisted for up to 25 My. We also find evidence that human, chimpanzee, and gorilla louse endosymbionts have lost a pathway for synthesis of vitamin B1, whereas the monkey louse symbiont has retained this pathway. It is unclear whether these changes are adaptive, but they may point to evolutionary responses of louse symbionts to shifts in primate biology.
Acute Large-Bowel Obstruction in an Institutionalized Man
Authors: Arianna Birindelli, Franca Patrizi, Salomone Di Saverio
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Efficacy of <i>Pseudomonas aeruginosa</i> eradication regimens in bronchiectasis
Authors: Emilie Vallières, Karen Tumelty, Michael M. Tunney, Rosemary Hannah, Oonagh Hewitt, J. Stuart Elborn, Damian G. Downey
Journal: European Respiratory Journal (2017)

Patients with bronchiectasis and chronic infection with Pseudomonas aeruginosa have more frequent pulmonary exacerbations and hospital admissions, and reduced quality of life and survival, than those who are free of P. aeruginosa infection [1]. Guidelines published by the British Thoracic Society recommend treatment to eradicate P. aeruginosa when first isolated in respiratory tract samples of people with bronchiectasis [2]. However, the best regimen to achieve eradication and how to determine successful eradication are yet unknown. Combining inhaled and systemic antibiotics appears superior for eradication of P. aeruginosa in bronchiectasis <http://ow.ly/UpMn309KfMQ>
No Association of EBV or Immunosuppression Status with Outcomes in US Patients with Diffuse Large B-Cell Lymphoma Treated in the Immunochemotherapy Era
Authors: Sean I. Tracy, Thomas M. Habermann, Andrew L Feldman, Matthew J Maurer, Ahmet Dogan, Usha S Perepu, Sergei Syrbu, Stephen Ansell, Carrie A Thompson, George J Weiner, Cristine Allmer, Susan L. Slager, Thomas E. Witzig, James R Cerhan, Brian K Link
Journal: Blood (2016)
Monitoring Daily Dynamics of Early Tumor Response to Targeted Therapy by Detecting Circulating Tumor DNA in Urine
Authors: Hatim Husain, Vladislava O. Melnikova, Karena Kosco, Brian Woodward, Soham More, Sandeep C. Pingle, Elizabeth Weihe, Ben Ho Park, Muneesh Tewari, Mark G. Erlander, Ezra Cohen, Scott M. Lippman, Razelle Kurzrock
Journal: Clinical Cancer Research (2017)

Noninvasive drug biomarkers for the early assessment of tumor response can enable adaptive therapeutic decision-making and proof-of-concept studies for investigational drugs. Circulating tumor DNA (ctDNA) is released into the circulation by tumor cell turnover and has been shown to be detectable in urine.
Mental illness and injuries: emerging health challenges of urbanisation in South Asia
Authors: Devaki Nambiar, Junaid Razzak, Kaosar Afsana, Alayne M Adams, Arif Hasan, Dinesh Mohan, Vikram Patel
Journal: BMJ (2017)

Rapid unplanned urbanisation in South Asia has overlooked the health needs of poor and marginalised people. <b>Devaki Nambiar and colleagues</b> examine the problems of mental illness and injuries, and call for renewed political and financial commitment to urban health
The Microbiome of the Prostate Tumor Microenvironment
Authors: Ilaria Cavarretta, Roberto Ferrarese, Walter Cazzaniga, Diego Saita, Roberta Lucianò, Elisa R. Ceresola, Irene Locatelli, Laura Visconti, Giovanni Lavorgna, Alberto Briganti, Manuela Nebuloni, Claudio Doglioni, Massimo Clementi, Francesco Montorsi, Filippo Canducci, Andrea Salonia
Journal: European Urology (2017)
Inaccurate Claims About VA Surgical Quality Might Mislead Veterans
Authors: William B. Weeks
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Treatment response and outcomes of grade 3 (G3) pancreatic neuroendocrine carcinomas (HGNEC) based on pathologic differentiation.
Authors: Nitya Prabhakar Raj, Emily Valentino, Laura H. Tang, Marinela Capanu, Olca Basturk, David Klimstra, Diane Lauren Reidy
Journal: Journal of Clinical Oncology (2015)

e15185 Background: World Health Organization criteria define HGNEC as neuroendocrine tumors with Ki-67 index > 20%. However, it is unknown if treatment response and/or outcomes vary based on cellular differentiation (i.e., well differentiated (WDNEC) versus (vs) poorly differentiated (PDNEC)). We conducted a retrospective review of metastatic pancreatic HGNEC treated at Memorial Sloan Kettering Cancer Center to evaluate response to therapy, progression free survival (PFS), and overall survival (OS). Methods: Patients (pts) with G3 pancreatic WDNEC or PDNEC treated from 2000-2014 were identified. Demographics, response to 3 lines of systemic therapy (by RECIST criteria based on radiology reports), PFS, and OS were determined. Results: 45 pts were identified, 16 WDNEC (mean age 46.8, 43.8% male, 93.3% octreoscan positive in 14/15 pts tested) and 29 PDNEC (mean age 58.2, 65.5% male, 45.5% octreoscan positive in 5/11 pts tested). Median OS was 52.0 months in WDNEC vs 10.1 months in PDNEC (p = 0.0009). 10/16 (62.5%) WDNEC received platinum agents, 1/10 (10.0%) with partial response (PR), 5/10 (50.0%) with stable disease (SD), and 4/10 (40.0%) with progressive disease (PD). 27/29 (93.1%) PDNEC received platinum agents, 1/27 (3.7%) with complete response, 9/27 (33.3%) with PR, 10/27 (37.0%) with SD, and 7/27 (25.9%) with PD. Median PFS was 4.4 months for WDNEC vs 3.3 months for PDNEC (p = 0.16). 12/16 (75.0%) WDNEC received alkylating agents, 6/12 (50.0%) with PR, 3/12 (25.0%) with SD, 3/12 (25.0%) with PD. 6/29 (20.7%) PDNEC received alkylating agents, 3/6 (50.0%) with PR, 1/6 (16.7%) with SD, 2/6 (33.3%) with PD. Median PFS was 5.6 months for WDNEC vs 4.2 months for PDNEC (p = 0.27). 6/16 (37.5%) WDNEC received targeted agents, 1/6 (16.7%) with SD and 5/6 (83.3%) with PD. 1/29 (3.4%) PDNEC received a targeted agent; this pt had a PR. 3/16 (18.8%) WDNEC received octreotide therapy, 1/3 (33.3%) with SD, 2/3 (66.7%) with PD, median PFS 6.2 months. Conclusions: In this series, WDNEC had significantly improved OS compared to PDNEC. Both WDNEC and PDNEC responded to alkylating agents; PDNEC had a higher response to platinum agents. Targeted agents were rarely used with a signal of activity noted in few pts.
Recent Advances In Nuclear Medicine.
Journal: Annals of Internal Medicine (1975)

This volume, designed primarily for the nuclear medical expert, is organized in the broad categories of instrumentation, dynamic function studies, radiopharmaceuticals and dosimetry, and organ scanning; but it really represents a series of concise odes in nuclear medicine. As a result, the reader looking for information on a specific topic will be rewarded if his subject is included in this text. And even though many of the papers are but brief discussions, the bibliographies are in general good enough so that the volume will frequently serve as a place to start. In contrast to much of the current literature which emphasizes radioisotope scanning, perhaps the strongest section of this work is that
The Value of Cancer Immunotherapy Summit at the 2016 Society for Immunotherapy of Cancer 31st Anniversary Annual Meeting
Authors: Howard L. Kaufman, Michael B. Atkins, Adam P. Dicker, Heather S. Jim, Louis P. Garrison, Roy S. Herbst, William T. McGivney, Steven Silverstein, Jon M. Wigginton, Peter P. Yu
Journal: Journal for ImmunoTherapy of Cancer (2017)

As healthcare costs continue to rise, there has been great interest in understanding and defining the value of current therapeutic strategies for the treatment of cancer. Cancer immunotherapy has emerged as a clinically beneficial alternative to conventional therapies for a variety of malignancies. Characterized by broad clinical activity, durable response rates, distinct side effects, and unique response kinetics, immune-based agents are vastly different compared with traditional cytotoxic or targeted therapies. To date, however, value assessments in oncology have not focused on the unique aspects of cancer immunotherapy, which has resulted in a lack of understanding of the true value of these therapies. Therefore, the Society for Immunotherapy of Cancer (SITC) convened key stakeholders to address the critical issues that define the value of cancer immunotherapy in National Harbor, Maryland on November 13, 2016. Organized in collaboration with the American Society for Clinical Oncology (ASCO) and with over 1500 registrants, this Value of Cancer Immunotherapy Summit united research scientists, academic physicians, industry professionals, health economists, third-party payers, and patients to discuss critical issues surrounding the value framework for cancer immunotherapy. This half-day summit addressed the current landscape of cancer therapy value models, economic outcomes, the current status of predictive biomarkers, as well as presentations from third-party payers, industry representatives, patient outcome experts, and patient advocacy groups to gain their perspectives on the value of cancer immunotherapy. Here, we summarize the presentations and the dominant themes from this symposium, with the intention of providing insight on future directions and to develop recommendations to better define the value of cancer immunotherapy for patients with cancer.
Remodelling in the bronchial mucosa in very young children with high risk for developing asthma
Authors: Katarina Urbanova, Petr Pohunek, Jiri Uhlik
Journal: European Respiratory Journal (2011)

Remodelling of the bronchial wall was thought to be a typical characteristic for asthma and the result of chronic inflammation. Structural changes were documented in bronchial mucosa of preschool children treated for asthma. We have very limited knowledge about the onset of these changes in small children. The course of wheezing disorders in young age cannot be reliably predicted, so it is difficult to identify the most probable candidates for developing asthma.  The aim of our study is to identify abnormalitites in the bronchial wall in children with high-risk of developing asthma. We examined endobronchial biopsies from 23 children under 4 years of age undergoing flexible bronchoscopy for clinical reasons others than recurrent wheezing. Twelve children fulfiled the criteria of Asthma Predictive Index, eleven children were in the control group. Thickness of the basement membrane was significantly higher in the high risk group than in the controls (on the average 4.14 μm vs. 3.53 μm respectively). On the other side, there seems to be no significant difference in the presence of neutrophil leucocytes and myofibroblasts between the two groups. This may correlate with the fact that all the patients were suffering from chronic or repeated respiratory problems for which they were indicated to bronchoscopy. However we suggest that first signs of remodelling like thickening of the basement membrane can be already present in children with high-risk of developing asthma in very early age. This may help us to improve therapeutic interventions in these children to prevent further development of irreversible morphological changes in later age. Supported by IGA MH CR No. NT 11444 and NT 11459.
Implantable Cardioverter-Defibrillators With Versus Without Resynchronization Therapy in Patients With a QRS Duration &gt;180 ms
Authors: Varun Sundaram, Jayakumar Sahadevan, Albert L. Waldo, George J. Stukenborg, Yogesh N.V. Reddy, Samuel J. Asirvatham, Judith A. Mackall, Anselma Intini, Brigid Wilson, Daniel I. Simon, Kenneth C. Bilchick
Journal: Journal of the American College of Cardiology (2017)
iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases
Authors: Edsel M. Abud, Ricardo N. Ramirez, Eric S. Martinez, Luke M. Healy, Cecilia H.H. Nguyen, Sean A. Newman, Andriy V. Yeromin, Vanessa M. Scarfone, Samuel E. Marsh, Cristhian Fimbres, Chad A. Caraway, Gianna M. Fote, Abdullah M. Madany, Anshu Agrawal, Rakez Kayed, Karen H. Gylys, Michael D. Cahalan, Brian J. Cummings, Jack P. Antel, Ali Mortazavi, Monica J. Carson, Wayne W. Poon, Mathew Blurton-Jones
Journal: Neuron (2017)
Inhaled efficacious dose translation from rodent to human: A retrospective analysis of clinical standards for respiratory diseases
Authors: J.E. Phillips
Journal: Pharmacology & Therapeutics (2017)

Clinical pharmacologists and toxicologists are often faced with predicting equivalent dosages for humans from biological observations in laboratory animals. Allometric scaling has been used extensively as the basis for extrapolation of drug dosage that might be expected to produce the equivalent biological effects. Allometry is the study of size and its consequences and it is based on the anatomical, physiological, and biochemical similarities between animals. In this review, retrospective analyses have been performed based on data reported in the literature in an attempt to determine the utility of allometric scaling for human dose projections from pre-clinical data for compounds that are delivered by inhalation. The limited pre-clinical efficacy data available on inhaled drugs that are also used clinically supports the current method of scaling using a fixed allometric exponent of 0.67. An example of the utility of the human inhaled dose projections for planning inhaled toxicology studies is also presented.
Xenotransplantation of layer-by-layer encapsulated non-human primate islets with a specified immunosuppressive drug protocol
Authors: Muhammad R. Haque, Jiwoong Kim, Hyojun Park, Han Sin Lee, Kyo Won Lee, Taslim A. Al-Hilal, Jee-Heon Jeong, Cheol-Hee Ahn, Doo Sung Lee, Sung Joo Kim, Youngro Byun
Journal: Journal of Controlled Release (2017)