tbuckley/cabot-search huggingface dataset:
Meta-analysis of the pharmacokinetic variability of liposomal anticancer agents compared with nonliposomal anticancer agents.
Authors: B. Sidone, B. A. Zamboni, W. Zamboni
Journal: Journal of Clinical Oncology (2011)

2583 Background: There appears to be significant interpatient variability in the pharmacokinetic (PK) disposition of liposomal-encapsulated anticancer agents. The interpatient PK variability of carrier-mediated agents is suspected to be associated with the patient's mononuclear phagocyte system (MPS), age, and/or body composition. However, the variability between liposomal agents compared with nonliposomal agents has not been systematically evaluated. Methods: A systematic review and meta-analysis was conducted utilizing PubMed (1966-2011) in addition to manual searches of reference sections of key articles. Phase I, II, and III studies that included PK studies were included in our analysis. The mean ± SD, CV%, and range of area under the concentration versus time curves (AUC) were collected for 18 nonliposomal and liposomal formulations of the same anticancer agents. The ratio of AUC CV% of the liposomal formulation to the nonliposomal formulation of the same drug at similar doses was calculated. The ratio of AUCmax to AUCmin of the liposomal formulation to the nonliposomal formulation of the same drug was also calculated. Results: The AUC CV% and ratio of AUCmax to AUCmin for liposomal and nonliposomal anticancer agents are included. Conclusions: The PK variability of liposomal agents was 2.7-fold (P<0.001) and 16.7-fold (P=0.13) greater than non-liposomal agents as measured by ratio of AUC CV% and ratio of AUCmax to AUCmin, respectively. Our results support the need to identify factors associated with the significant PK variability of liposomal agents. This may be accomplished through the development of phenotypic probes that can be used to measure MPS function. Similar systematic analysis also needs to be performed for other carrier-mediated agents. AUC CV% (n=18) Ratio of AUCmax to AUCmin (n=11) Liposomal agent Nonliposomal agent Ratio of liposomal to nonliposomal Liposomal agent Nonliposomal agent Ratio of liposomal to nonliposomal Mean 65.6 30.7 2.7 34.1 3.6 16.7 SD 18.6 16.0 2.0 41.9 1.8 21.5 CV% 28% 52% 72% 123% 51% 129% Min 39 12 1.2 2.7 2.1 0.7 Max 85 69 7.1 113.5 6.6 53.5
Short-Term Results of Laparoscopic Radiofrequency Ablation Using a Multipolar System for Localized Hepatocellular Carcinoma
Authors: Naoki Morimoto, Norio Isoda, Yoshinari Takaoka, Takuya Hirosawa, Shunji Watanabe, Toshiya Otake, Kozue Murayama, Takeshi Fujieda, Mamiko Tsukui, Natsumi Miyata, Kohei Ono, Shota Yamaguchi, Hironori Yamamoto
Journal: Liver Cancer (2016)

&lt;b&gt;&lt;i&gt;Background and Aim:&lt;/i&gt;&lt;/b&gt; Multipolar radiofrequency ablation (RFA) is feasible for the treatment of hepatocellular carcinoma (HCC) for which a large ablative area is planned, and it imposes a light physical burden on patients. Multipolar RFA via the percutaneous approach is performed in the majority of cases, but the efficacy of multipolar RFA with a laparoscopic approach has rarely been studied. This study aimed to evaluate the efficacy and safety of multipolar laparoscopic RFA (LRA) for localized HCC over the short term. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; From January 2014 to January 2016, 77 consecutive patients with 130 HCCs treated by multipolar LRA were assessed. One to three bipolar needle applicators were inserted under laparoscopic ultrasonography guidance, regardless of tumor location. We intended to achieve parallel insertions and no-touch ablation as much as possible. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The median size of the main tumor was 22 mm (range, 10-42 mm). The median follow-up time was 13.6 months (range, 3.1-24.8 months). In all cases, a sufficient ablative area was obtained as planned, without thermal injury of adjacent organs. During the follow-up period, all patients were alive with no local tumor progression, while intrahepatic recurrence distant from the primary site occurred in 7 patients. The 2-year local tumor progression-free survival rate and overall cancer-free survival rate were 100 and 81.6%, respectively. There were no procedural major complications caused prolonging the hospitalization, and all patients were discharged without subjective symptoms 4-7 days after LRA. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Multipolar LRA was efficacious in the treatment of localized HCCs by safely achieving a good ablative area.
Split Mixed Donor Chimerism Early after T-Cell Depleted Reduced Intensity Conditioned Allogeneic Haematopoietic Stem Cell Transplantation Predicts Survival
Authors: Francesca A M Kinsella, Amy Gudger, Charlotte F Inman, Graham Mc Ilroy, Sandeep Nagra, Jane Nunnick, Dave Waldron, Kerry Wall, Mike Griffiths, Paul Moss, Charles Craddock, Emmanouil Nikolousis, Ram Malladi
Journal: Blood (2014)
3D Bioprinting for Organ Regeneration
Authors: Haitao Cui, Margaret Nowicki, John P. Fisher, Lijie Grace Zhang
Journal: Advanced Healthcare Materials (2016)

Regenerative medicine holds the promise of engineering functional tissues or organs to heal or replace abnormal and necrotic tissues/organs, offering hope for filling the gap between organ shortage and transplantation needs. Three‐dimensional (3D) bioprinting is evolving into an unparalleled biomanufacturing technology due to its high‐integration potential for patient‐specific designs, precise and rapid manufacturing capabilities with high resolution, and unprecedented versatility. It enables precise control over multiple compositions, spatial distributions, and architectural accuracy/complexity, therefore achieving effective recapitulation of microstructure, architecture, mechanical properties, and biological functions of target tissues and organs. Here we provide an overview of recent advances in 3D bioprinting technology, as well as design concepts of bioinks suitable for the bioprinting process. We focus on the applications of this technology for engineering living organs, focusing more specifically on vasculature, neural networks, the heart and liver. We conclude with current challenges and the technical perspective for further development of 3D organ bioprinting.
De-novo EGFR mutation and MET amplification in NSCLC with crizotinib response; a case against one-gene/one-drug paradigm
Authors: Simon Y-R. Ang, Miah-Hiang Tay, Eunice B-J. Ng, Peter C-S. Ang, Benjamin Y-S. Chuah
Journal: Annals of Oncology (2015)
263. A Novel Peptide-Grafted AAV Capsid Exhibits Enhanced CNS Transduction in Both Adult Mice and Cat, as Well as SOD1 Knockdown in Adult hSOD1 ALS Mice
Authors: Sourav Choudhury, Lorelei Stoica, Anne F. Harris, Damien Cabral, Heather L. Gray-Edwards, Jacob A. Johnson, Aime K. Johnson, Douglas R. Martin, Miguel Sena-Esteves
Journal: Molecular Therapy (2015)

Effective gene transfer to CNS is key for development of new therapies for neurological diseases. Relatively few natural AAV capsids cross the blood-brain barrier (BBB) upon systemic infusion and even then, transduction in adult brain after systemic delivery is limited to mainly glia and endothelium. Here we report the CNS tropism of a new AAV vector generated by genetic grafting of a small peptide into the capsid of AAV9.47, a liver-detargeted AAV9 mutant. The peptide insertion was tolerated well with no loss of packaging efficiency compared to AAV9.47 or AAV9. The scAAV-CBA-GFP vectors were infused via the tail vein in 6-8 week-old C57BL/6 mice at 5E11 vg. The new AAV vector transduced cortical and striatal neurons in the brain at high efficiency, as well as motor neurons and interneurons in the spinal cord. Significantly more vector genomes were found in the cerebrum (15-fold) and spinal cord (6-fold) compared to AAV9, while in peripheral tissues there were no significant differences. Western blot analysis of GFP expression levels confirmed the vector biodistribution results. Binding studies in parental and sialic acid-deficient CHO cells showed the interaction of the new AAV vector with terminal galactose to be unchanged compared to AAV9. The CNS tropism of the new AAV vector was evaluated in a 4 week-old cat infused with 1.26E13 vg via the carotid artery. Similar to the results in adult mice, the new AAV vector transduced cortical and striatal neurons in feline brain, and motor neurons in the feline spinal cord. These results suggest the remarkable CNS transduction properties of the new AAV may translate to higher organisms. Finally, we used the new AAV vector to knock down expression of human SOD1 in SOD1G93A mouse model of familial ALS. For these studies we used a self-complementary AAV vector encoding an artificial microRNA against human SOD1 in the 3'UTR of a CBA-GFP expression cassette. The scAAV-CBA-GFP-miR vector was infused via the tail vein in 55-day old SOD1G93A mice at 5E11 vg. At 4 weeks post-injection, there was 20% reduction in hSOD1 mRNA in the thoracic spinal cord of mice infused with the new AAV vector. The enhanced CNS targeting properties of the new AAV vector make it a promising candidate for gene therapy of neurodegenerative disorders.
Abstract 4209: Development of patient-derived xenograft (PDX) models for small cell lung cancer (SCLC) as a preclinical platform for drug development
Authors: Chelsea Mullins, Jill Ricono, Praveen Nair, Cyrus Mirsaidi, Thomas Broudy
Journal: Cancer Research (2015)

Abstract Small cell lung cancer comprises 15-20% of all lung cancer cases, is very invasive with a high mortality rate. Although SCLC patients respond to chemotherapy, there is a high rate of recurrence with treated patients and those in advanced stage of the disease often have a refractory response to treatment. As such, the need for new treatment modalities is critical. In this work, we describe the development and characterization including histopathology, IHC and mutational analysis of 8 SCLC PDX models established from a collection of &amp;gt;300 small cell lung cancer specimens, many of which come from prior-treated and metastatic patients. We have also evaluated functional response of these models with in vivo pharmacology studies. Our data demonstrates the potential to use these unique PDX models in drug development for treatment of SCLC. Citation Format: Chelsea Mullins, Jill Ricono, Praveen Nair, Cyrus Mirsaidi, Thomas Broudy. Development of patient-derived xenograft (PDX) models for small cell lung cancer (SCLC) as a preclinical platform for drug development. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4209. doi:10.1158/1538-7445.AM2015-4209
PTH-025 Does increasing numbers of gastroscopies increase the yield of upper gastrointestinal cancers? A 6-year survey of 20 000 gastrocopies
Authors: S Shaukat, J Landy, A King, S Catnach, I Barrison
Journal: Gut (2010)

<h3>Introduction</h3> The number of upper gastrointestinal endoscopies performed has increased significantly since the introduction of 2-week wait targets and open access endoscopy services. It is not clear whether this has led to an increase in the detection of significant lesions such as upper gastrointestinal cancers.1 We aimed to assess the detection rates of oesophageal and gastric carcinoma between 2003 and 2008 in relation to gastroscopy rates over the same period. <h3>Methods</h3> The endoscopy (Infoflex) database was searched for all diagnoses of oesophageal and gastric carcinoma between January 2003 and December 2008. Repeat procedures or procedures not identified as new diagnoses were excluded. Incidence rates were calculated adjusting for total endoscopy rates per year. 95% CIs were calculated and R squared values (r<sup>2</sup>) were fitted using the method of least squares to identify time trends and to measure the appropriateness of fitting to a linear model. <h3>Results</h3> 20 642 patients underwent upper gastrointestinal endoscopy between 2003 and 2008. The number of upper gastrointestinal endoscopies performed each year increased steadily from 2438 procedures in 2003 to 4029 procedures in 2008 (r<sup>2</sup> 0.74). The number of oesophageal cancers detected steadily increased between 2003 and 2008 from 38 (95% CI 35.4 to 40.6) to 60 (95% CI 57.9 to 62.1) (r<sup>2</sup> 0.63). Adjusting for the increase in endoscopy rates over the same period there was no increase in the rates of diagnosis of oesophageal cancer; 15.6 (95% CI 14.4 to 16.8) in 2003 to 14.9 (95% CI 13.7 to 16.1) in 2008, (r<sup>2</sup> 0.17). The number of gastric cancers remained constant between 2003 and 2008; 26 (95% CI 22.3 to 29.7) in 2003 to 30 (95% CI 26.6 to 33.4) in 2008 (r<sup>2</sup> 0.0003). Adjusting for the increase in endoscopy rates over the same period there was a slight decrease in the rates of diagnosis of gastric cancers although no clear trend was demonstrated; 10.7 (95% CI 9 to 12.3) in 2003 to 7.4 (95% CI 5.5 to 9.4) in 2008 (r<sup>2</sup> 0.2). <h3>Conclusion</h3> The numbers of gastroscopies performed have steadily increased between 2003 and 2008. The increase in endoscopy rates has been mirrored by an increase in the diagnosis of oesophageal cancer. The rates of diagnosis of gastric cancer has not increased despite the increase in endoscopy rates. Increased rates of gastroscopy may improve detection rates of oesophageal carcinoma, but have not led to an increase in detection of gastric cancer.
Abstract 4272: Potent <i>in situ</i> cancer immunotherapy with synthetic human STING-activating cyclic dinucleotides
Authors: Laura Hix Glickman, David B. Kanne, Kelsey E. Gauthier, George E. Katibah, Justin J. Leong, Ken Metchette, Thomas W. Dubensky, Sarah M. McWhirter
Journal: Cancer Research (2015)

Abstract Spontaneous tumor-initiated T cell priming is dependent on IFN-β production by tumor-resident dendritic cells. Based on recent observations indicating that IFN-β expression was dependent upon activation of the host STING (Stimulator of Interferon Genes) pathway, we hypothesized that direct engagement of STING through intratumoral administration of specific agonists would result in effective anti-tumor therapy. To this end, we generated novel synthetic cyclic dinucleotide (CDN) derivatives with superior STING-activating and anti-tumor properties. The most potent molecule contains a 2′-5′ and 3′-5′ phosphate bridge that increases its affinity for STING at least 10-fold. Additionally, sulfur atoms at the non-bridging oxygens of the internucleotide phosphate bridge enable both superior STING binding affinity, as well as resistance to host cell phosphodiesterases. Importantly, the lead molecule activates PBMCs from a panel of human donors representing all known STING alleles, including homozygotes for the most refractory allele. Intratumoral injection of the lead CDN molecule induced profound regression of established B16 melanoma tumors, generated substantial systemic immune responses capable of rejecting distant metastases and provided long-lived immunologic memory. Cures in entire cohorts of mice bearing well-established 4T1 mammary and CT26 colon carcinoma models correlated with induction of cytokine-mediated innate and adaptive antigen-specific T cell immunity, both systemically and in the tumor microenvironment. Immune activation and anti-tumor efficacy was lost in mice encoding non-functional STING. In vivo activation of STING with the lead CDN administered by multiple routes demonstrated a high safety and tolerability margin in preclinical toxicology studies. In addition, pharmacokinetic analysis indicates that the lead CDN compound was rapidly cleared from systemic circulation, consistent with pulsatile STING activation and transient systemic cytokine and hematological changes. These results demonstrate that CDNs have high translation potential for treatment strategies to induce activation of the tumor microenvironment, leading to effective tumor-initiated T cell priming and anti-tumor immunity. Citation Format: Laura Hix Glickman, David B. Kanne, Kelsey E. Gauthier, George E. Katibah, Justin J. Leong, Ken Metchette, Thomas W. Dubensky, Sarah M. McWhirter. Potent in situ cancer immunotherapy with synthetic human STING-activating cyclic dinucleotides. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4272. doi:10.1158/1538-7445.AM2015-4272
Association of High Levels of Free Light Chain and the Presence of Igh Translocations in Multiple Myeloma and Prognostic Implications.
Authors: Shaji Kumar, Lijun Zhang, Angela Dispenzieri, Scott Van Wier, Jerry Katzmann, Melissa Snyder, Emily Blood, Roberta DeGoey, Kim Henderson, Arthur Bradwell, Robert Kyle, Philip Greipp, S. Vincent Rajkumar, Rafael Fonseca
Journal: Blood (2008)
Comparable Survival Outcome with a Faster Engraftment of HSCT from a Haploidentical Donor Compared to Other Donor Types in Pediatric Acquired Aplastic Anemia
Authors: Ho Joon Im, Hyery Kim, Sung-Han Kang, Eun Seok Choi, Kyung-Nam Koh, Jong Jin Seo, Young-Uk Cho, Seongsoo Jang, Seog Woon Kwon, Chan-Jeoung Park, Jin Kyung Suh
Journal: Blood (2016)
Gas6 and Its Receptors Are Implicated in Sepsis as Modulators of Innate Immunity.
Authors: Laurent Burnier, Rocco Sugamele, Didier Le Roy, Thierry Roger, Thierry Fumeaux, Marc Chanson, Delphine Borgel, Greg Lemke, Glenn K. Matsushima, H. Shelton Earp, Peter Carmeliet, Marc Schapira, François Feihl, Thierry Calandra, Anne Angelillo-Scherrer
Journal: Blood (2007)
Abstract 3721: Rapid widening of age and race health disparities in prostate cancer outcomes within the United States, 1973-2014
Authors: Richard J. Lawrence, Damien Urban, Talia Golan, Akram Saad, Raanan Berger, Raya Leibowitz-Amit, Jair Bar, Robert Den, Jeffrey Goldstein, Zvi Symon
Journal: Cancer Research (2015)

Abstract Introduction Little is known concerning how cancer-outcome disparities have changed over time. We investigated how age and race disparities in prostate cancer (PCa) survival have changed in the USA over the last 40 years. Methods We utilized the SEER database to track PCa outcomes. Incl. criteria: subjects with PCa diagnosed 1973 - 2008, aged 50-89 yrs. Excl. criteria: multiple primary cancers, unknown stage. Results 658,916 PCa patients were analyzed. Median follow up for alive patients was 54m (interquart. range 39-75m). Median age of diagnosis decreased from 73 to 60 yrs from 1973 to 2008, and the proportion aged &amp;gt; = 70 yrs decreased from 62% to 40%. The proportion diagnosed with metastatic disease decreased from 18% to 4%; likewise amongst those with M0 disease the proportion with T3-4 decreased from 41% to 17%. The remainder of the results are confined to M0 disease. Four-year cancer specific death decreased progressively for all age groups. But whereas 4 year cancer specific mortality dropped from 24% to 3% in those aged 50-54, it only decreased from 38% to 18% in those aged 85-89. Whereas the hazard ratio (HR) for cancer-specific death for those aged 85-89 (50-54 year old subjects reference group) was 1.6 in 1973-9, in 2000-8 it was 10.9 (table). The widening age disparities were only marginally altered by incorporation of ‘tumor stage’ into the model. Similar widening age disparities were seen in metastatic disease. Race-related disparities also widened over the study period; the HR for death increasing from 1.1 (1973-79) to 1.3 (2000-8). Hazard ratios for prostate cancer-specific death stratified by year of diagnosis, stage M0Age1973-91980-91990-92000-950-4111155-91.11.01.11.060-41.11.11.51.265-91.11.11.81.670-41.21.22.22.375-91.21.32.93.580-41.41.53.86.185-91.61.75.010.9 Conclusions Age- and Race- related health disparities in survival outcomes in both metastatic and non-metastatic prostate cancer have greatly widened over the past 40 years; this effect appears to be accelerating and is not explained by delayed diagnosis. Since outcome disparities have grown against a backdrop of improved screening, diagnosis and treatment, it appears that measures targeted at these populations will be needed in order to redress the imbalance. Citation Format: Richard J. Lawrence, Damien Urban, Talia Golan, Akram Saad, Raanan Berger, Raya Leibowitz-Amit, Jair Bar, Robert Den, Jeffrey Goldstein, Zvi Symon. Rapid widening of age and race health disparities in prostate cancer outcomes within the United States, 1973-2014. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3721. doi:10.1158/1538-7445.AM2015-3721
Annals Consult Guys - Postoperative Calf Venous Thrombosis: Location, Location, Location
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2016)

Web Exclusives20 December 2016Annals Consult Guys - Postoperative Calf Venous Thrombosis: Location, Location, LocationFREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author and Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W16-0012 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Annals Consult Guys brings a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Janssen, Portola; Consultancies: Bristol-Myers Squibb, Janssen. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 December 2016Volume 165, Issue 12Page: CG1KeywordsDisclosureResearch grantsResearch reporting guidelinesThrombosis ePublished: 20 December 2016 Issue Published: 20 December 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.Loading ...