tbuckley/cabot-search huggingface dataset:
Pharmacological macrophage inhibition decreases metastasis formation in a genetic model of pancreatic cancer
Authors: Heidi Griesmann, Christof Drexel, Nada Milosevic, Bence Sipos, Jonas Rosendahl, Thomas M Gress, Patrick Michl
Journal: Gut (2016)

Objectives Tumour-associated macrophages play an important role in mediating tumour progression. In pancreatic cancer, infiltrating macrophages are known to mediate tumour progression and have been identified in invasive tumours and in early preinvasive pancreatic intraepithelial precursor lesions. We aimed to study the impact of pharmacological macrophage depletion by liposomal clodronate in a genetic mouse model of pancreatic cancer. Methods KPC mice ( LSL-Kras G12D/+ ;LSL-Trp53 R172H/+ ;Pdx-1-Cre ) were treated for 12 weeks with liposomal clodronate or control liposomes. Tumour and metastasis formation as well as alterations in local and circulating immune cells and cytokines were analysed. Results Treatment with liposomal clodronate effectively reduced CD11b-positive macrophages both in the pancreas and other organs such as liver, lung and spleen. While tumour incidence and growth were only slightly reduced, metastasis formation in the liver and lungs was significantly diminished after macrophage depletion. This antimetastatic effect was independent of the presence of an endogenous primary tumour, since reduced pulmonary colonisation was also detected in clodronate-pretreated mice after tail vein injection of syngeneic pancreatic cancer cell lines. Macrophage inhibition by liposomal clodronate was associated with significantly impaired angiogenesis, reduced circulating vascular endothelial growth factor levels and decreased circulating CD4+CD25+ T cells. These alterations could be confirmed in an independent macrophage depletion model using CD11b-diphtheria toxin receptor mice. Conclusions Pharmacological depletion of macrophages in a genetic mouse model of pancreatic cancer markedly reduced metastasis formation and is associated with impaired angiogenesis and reduced CD4+CD25+ T cell levels. Pharmacological targeting of infiltrating macrophages represents a promising novel tool for antimetastatic therapeutic approaches.
Incidental germline variants in 1000 advanced cancers on a prospective somatic genomic profiling protocol
Authors: F. Meric-Bernstam, L. Brusco, M. Daniels, C. Wathoo, A.M. Bailey, L. Strong, K. Shaw, K. Lu, Y. Qi, H. Zhao, H. Lara-Guerra, J. Litton, B. Arun, A.K. Eterovic, U. Aytac, M. Routbort, V. Subbiah, F. Janku, M.A. Davies, S. Kopetz, J. Mendelsohn, G.B. Mills, K. Chen
Journal: Annals of Oncology (2016)
Only patients with BP below 160/100 should be referred for surgery to avoid cancellations, guidelines say
Authors: Susan Mayor
Journal: BMJ (2016)

GPs should include information on a patient’s blood pressure (BP) in referral letters for elective surgery and should refer only those with BP lower than 160/100 mm Hg over the previous 12 months, say new guidelines that aim to reduce surgery cancellations due to high BP.1

Nearly 1% of planned surgery in the NHS is currently cancelled at the last minute, and hypertension is a common reason.

“Across the UK this equates to approximately 100 concerned and inconvenienced patients each day, with associated costs to the NHS and the national economy,” said the co-chair of the guideline working party, Andrew Hartle, who is a consultant anaesthetist at St Mary’s Hospital in London and president of the …
Gluconeogenesis in the Tumor-Influenced Rat Hepatocyte: Importance of Tumor Burden, Lactate, Insulin, and Glucagon
Authors: R I Inculet, J L Peacock, C M Gorschboth, J A Norton
Journal: JNCI Journal of the National Cancer Institute (1987)

In an attempt to define the relationship between tumor burden (cachexia) and host hepatocyte gluconeogenesis, the following experiments were performed with the use of an F344 male rat bearing a transplantable sarcoma. Food intake of tumor-bearing (TB) rats was constant until day 24 following implant and a tumor burden of 18±5.2% (x̄± SD), at which time food intake progressively declined daily. Tumor burden was arbitrarily divided at 12.8% to determine if any measured changes occurred prior to or following the approximate time when a significant decline in food intake occurred. Plasma glucose levels decreased with tumor burden. Whole-blood lactate levels increased with tumor burden. Fasting plasma alanine levels decreased with tumor burden. Plasma 3-methylhistidine levels increased with tumor burden. Plasma glucagon levels increased with tumor burden, whereas plasma insulin levels decreased. Hormone changes were noted at small tumor burdens prior to a decline in food intake. Viable hepatocytes were isolated from 4 groups: non-tumor-bearing (NTB), small tumor burden [(STB) 3.5% total body weight (TBW)], moderate tumor burden [(MTB) 14% TBW], and large tumor burden [(LTB) 23% TBW]. As expected in NTB rats, hepatocytes produced significantly more glucose with 20 mM lactate than 20 mM alanine or than Hanks' balanced salt solution (HBSS) alone. Hepatocytes from STB rats demonstrated the same basic relationship for lactate, alanine, and HBSS, but they produced significantly more glucose from lactate and HBSS alone than NTB hepatocytes. With alanine as substrate, the rates of glucose production by hepatocytes were not affected by the presence or size of tumor. However, with lactate as substrate, hepatocytes from MTB and LTB rats produced progressively less glucose as tumor burden increased (r = − 0.85, P<.001), which may partly explain the reduction in blood glucose and elevation in blood lactate levels observed. Elevated gluconeogenesis in TB rats occurred early prior to a decline in food intake. The key precursor appeared to be lactate. The balance between glucagon and insulin appeared to promote the abnormal host carbohydrate metabolism observed.
Phase I, first-in-human trial of LV305 in patients with advanced or metastatic cancer expressing NY-ESO-1.
Authors: Neeta Somaiah, Matthew Stephen Block, Joseph W. Kim, Geoffrey Shapiro, Patrick Hwu, Joseph Paul Eder, Robin Lewis Jones, Sacha Gnjatic, Hailing Lu, Frank James Hsu, Seth Pollack
Journal: Journal of Clinical Oncology (2015)

3021 Background: Generation of tumor-specific cytotoxic T cells (CTLs) in vivo is a major goal of cancer immunotherapy. LV305 is a replication-incompetent, integration-deficient, hybrid viral vector based on the ZVex platform designed to target dendritic cells (DC) in vivo via CD209 (DC-SIGN) and induce the full-length expression of the cancer testis antigen, NY-ESO-1, in order to generate and expand anti-cancer CTLs. In preclinical models, LV305 is a potent inducer of CTLs and anti-tumor immunity. In this first-in-human study, the safety, immunogenicity and efficacy of LV305 are being examined in patients (pts) with cancer. Methods: Adults with previously treated, advanced or metastatic melanoma, sarcoma, breast, lung or ovarian cancers expressing the NY-ESO-1 protein by IHC were eligible. Following a 3+3 dose escalation design, 3 pts were enrolled into 4 cohorts to receive 3 or 4 intradermal injections every 3 weeks of 108, 109 or 1010 vector genomes (vg) per dose. Expansion of up to 53 pts at the 1010dose is underway. Results: During dose escalation, 12 pts with NY-ESO-1 positive sarcomas were treated. No DLT or SAEs were observed and all related AEs were CTCAE grade 1 or 2. Common AEs were fatigue (58%), injection site reaction (33%), and myalgia (33%). After review by an independent DSMB, the highest dose, 1010 vg, was determined to be safe. Immunogenicity data from the initial 6 pts at the low dose (108 vg) demonstrated increased NY-ESO-1-specific CD8 and/or CD4 T cells in 3 pts by ELISPOT, tetramer assay of unstimulated blood, and/or TCR sequencing of blood and TILs. Data indicate the induction of T cells to new epitopes and boosting of TIL TCR sequences in blood. Of these initial 6 pts, 4 had a best response of SD (range 12-34+ weeks) with 1 pt achieving regression of 13.8%, and 2 had PD. The 6 pts dosed at 109 and 1010vg are completing therapy. Conclusions: LV305 demonstrated acceptable safety at all doses up to 1010 vg. At the lowest dose, LV305 generated strong T cell responses and preliminary evidence of anti-tumor effect. Data from the mid and high dose are pending. These encouraging results will be followed by studies of LV305 (1010 vg) alone, in prime/boost with G305 (NY-ESO-1 protein-TLR4 agonist) and with anti-PD-1 therapy. Clinical trial information: NCT02122861.
Primary squamous cell carcinoma of the liver: a case report
Authors: Tae Kyung Yoo, Byung Ik Kim, Eun Na Han, Dong Hyung Kim, Jung Hee Yoo, Seung Jae Lee, Yong Kyun Cho, Hong Joo Kim
Journal: Clinical and Molecular Hepatology (2016)

Primary squamous cell carcinoma (SCC) of the liver is very rare, and few cases have been reported in Korea. Primary SCC of the liver is known to be associated with hepatic cysts and intrahepatic stones. A 71-year-old male was admitted to our hospital, and a abdominal computed tomography scan revealed a 10 × 6 cm mass in the liver. Analysis of a biopsy sample suggested SCC, and so our team performed a thorough workup to find the primary lesion, which was revealed hepatoma as a pure primary SCC of the liver with multiple distant metastases. The patient was treated with one cycle of radiotherapy, transferred to another hospital for hospice care, and then died 1 month after discharge.
Question About the Analysis of Missing Data and Identification of an Error—Reply
Authors: Xinli Li, Tracy Smith, William Gunnar
Journal: JAMA Surgery (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 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
Cyril Barry Burdett-Smith
Authors: Peter Burdett-Smith
Journal: BMJ (2016)

Cyril Barry Burdett-Smith was proud of being a “true” Cockney, born within the sound of Bow bells. He originally studied to follow his father as a civil servant, but gaining two scholarships allowed him to enter Charing Cross Hospital Medical School in 1941. Studying during the blitz was not easy, and everyone available was required to manage the casualties from the relentless bombing. After qualifying Barry worked …
Lung Carcinoma of Sheep (Jaagsiekte). Analysis of Free Amino Acids and Glucose Tolerance Tests 2
Authors: A. Zimber, I. Hod, T. A. Nobel, U. Klopfer, K. Perk
Journal: JNCI Journal of the National Cancer Institute (1977)

Data were collected during a 2½-year follow-up of sheep selected and isolated from a multiple-case herd with lung carcinoma. Eighteen animals were hypergammaglobullnemic for prolonged periods, and 3 of the sheep proved to carry the disease. On forced or deliberate postmortem examination, the other sheep demonstrated various chronic lung diseases with different degrees of severity. One offspring of the selected ewes showed 2 foci of lung carcinoma. The 3 ewes with lung carcinoma had diabetic (2) or slightly diabetic (1) glucose tolerance curves, as compared to normal sheep (case-free herd) of the same age and sex. There were 3 animals free of lung carcinoma, but with chronic lung disease or liver abscesses, that had also diabetic curves. An age-dependent pattern of glucose tolerance curve was obtained. Analysis of free amino acids in the lung revealed a marked decrease in glycine level in the tumor when compared to adjacent lung tissue from the same animal or to normal lung obtained from healthy sheep. Plasma glycine (as well as other amino acids) was decreased in the tumor-bearing animals. Glycine contributed about 25–30% of total plasma amino acids in sheep; alterations in glycine concentration determined in this study were thus quantitative. In lung carcinoma of sheep, glycine offered extensive use as a precursor of nucleic acids (purines), glycogen, and lecithin (a constituent of lung surfactant), the synthesis of all of which was increased in the tumor tissue as compared to normal lung tissue.
O106 : Therapeutic plasma exchange modulates innate immune activation and improves outcome in patients with acute liver failure
Authors: C. Bernsmeier, V.C. Patel, A. Singanayagam, M. Yuksel, X. Huang, C. Willars, W. Bernal, G. Auzinger, Y. Ma, F.S. Larsen, J.A. Wendon, C.G. Antoniades
Journal: Journal of Hepatology (2015)
Carcinogenic Effects of Diisopropanolnitrosamine in Sprague-Dawley Rats
Authors: Ulrich Mohr, Gerd Reznik, Parviz Pour
Journal: JNCI Journal of the National Cancer Institute (1977)

The carcinogenic effects of diisopropanolnitrosamine (DIPN) were tested in Sprague-Dawley rats and were then compared with results produced earlier by the same substance in Syrian hamsters. In addition to the similarities, several differences were noted; for example, DIPN caused pancreatic tumors in all the hamsters, but only 1 pancreatic tumor was observed among the 150 rats. Administration of DIPN to rats led to the development of neoplasms in the nasal and paranasal cavities, lungs, thyroid gland, esophagus, liver, and kidneys. The highest tumor incidence in rats was in the nasal cavities. Almost all the pulmonary neoplasms were malignant and were usually squamous cell carcinomas. We found a 15.4–50% incidence of malignant tumors of the thyroid gland; we also noted that thyroid neoplasms occurred at almost the same rate (36.4–50%) in the groups given 1/5, 1/10, and 1/20 the median lethal dose.
Effect of sunitinib treatment on mutations and methylation in metastatic renal cancer.
Authors: Grant Stewart, Christophe Van Neste, Alison Meynert, Colin Semple, Fiach O'Mahony, Alexander Laird, Alan Mackay, Geert Trooskens, Wim Van Criekinge, Tim De Meyer, Thomas Powles, David James Harrison
Journal: Journal of Clinical Oncology (2015)

492 Background: The effect of VEGF targeted agents on DNA mutations and epigenetic expression in metastatic clear cell renal cancer (mccRCC) has not been reported. We hypothesise that significant DNA mutations and methylation changes occur with treatment which may be associated with resistance. Methods: DNA was extracted from sequential frozen pairs of primary tumour tissue from 14 mccRCC patients, in the SuMR clinical trial (NCT01024205), at presentation (biopsy) and after 3-cycles of sunitinib (nephrectomy). Multiple biopsies were taken to assess for heterogeneity. Biopsy and nephrectomy samples were compared in untreated tumours as controls. Array CGH, Ion Torrent sequencing (48 key ccRCC genes were assessed [Table]), and methylCap-seq DNA methylation analysis were performed. Results: aCGH hierarchical clustering showed that samples from 2/14 patients clustered together (13%). There were no significant increase in copy number variations (CNVs) following treatment with sunitinib. For somatic mutations of the 48 key genes, there were no patients in whom all samples clustered together. Conversely, at methylation level, all samples for each patient clustered. Mean frequency of mutations in the key genes relative to normal kidney was identical for biopsy and nephrectomy samples (n=14 mutations). 12/48 genes had CNVs or mutations in ≥2 patients following treatment with sunitinib (table). VHL was the only gene with significant difference in methylation pre- and post-sunitinib therapy (FDR=0.077; logFC=-0.8734, hypermethylated following sunitinib therapy); there was no difference in VHL methylation pre- and post-renal artery clamping. Conclusions: Intratumoral heterogeneity was not apparent in DNA methylation, unlike DNA. This may facilitate in biomarker research. The significant increase in VHL methylation following sunitinib gives insight into possible mechanisms of resistance at an epigenetic level. [Table: see text]
Restoring oxidant signaling suppresses proarthritogenic T cell effector functions in rheumatoid arthritis
Authors: Zhen Yang, Yi Shen, Hisashi Oishi, Eric L. Matteson, Lu Tian, Jörg J. Goronzy, Cornelia M. Weyand
Journal: Science Translational Medicine (2016)

ROS deficiency promotes proinflammatory T cells in rheumatoid arthritis.
Changes in the Geographic Patterns of Heart Disease Mortality in the United States
Authors: Michele Casper, Michael R. Kramer, Harrison Quick, Linda J. Schieb, Adam S. Vaughan, Sophia Greer
Journal: Circulation (2016)

Although many studies have documented the dramatic declines in heart disease mortality in the United States at the national level, little attention has been given to the temporal changes in the geographic patterns of heart disease mortality.Age-adjusted and spatially smoothed county-level heart disease death rates were calculated for 2-year intervals from 1973 to 1974 to 2009 to 2010 for those aged ≥35 years. Heart disease deaths were defined according to the International Classification of Diseases codes for diseases of the heart in the eighth, ninth, and tenth revisions of the International Classification of Diseases. A fully Bayesian spatiotemporal model was used to produce precise rate estimates, even in counties with small populations. A substantial shift in the concentration of high-rate counties from the Northeast to the Deep South was observed, along with a concentration of slow-decline counties in the South and a nearly 2-fold increase in the geographic inequality among counties.The dramatic change in the geographic patterns of heart disease mortality during 40 years highlights the importance of small-area surveillance to reveal patterns that are hidden at the national level, gives communities the historical context for understanding their current burden of heart disease, and provides important clues for understanding the determinants of the geographic disparities in heart disease mortality.
Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS)
Authors: C. Christine Lee, Steve M. Watkins, Carlos Lorenzo, Lynne E. Wagenknecht, Dora Il’yasova, Yii-Der I. Chen, Steven M. Haffner, Anthony J. Hanley
Journal: Diabetes Care (2016)

Recent studies using untargeted metabolomics approaches have suggested that plasma branched-chain amino acids (BCAAs) are associated with incident diabetes. However, little is known about the role of plasma BCAAs in metabolic abnormalities underlying diabetes and whether these relationships are consistent across ethnic populations at high risk for diabetes. We investigated the associations of BCAAs with insulin sensitivity (SI), acute insulin response (AIR), and metabolic clearance of insulin (MCRI) in a multiethnic cohort.In 685 participants without diabetes of the Insulin Resistance Atherosclerosis Study (IRAS) (290 Caucasians, 165 African Americans, and 230 Hispanics), we measured plasma BCAAs (sum of valine, leucine, and isoleucine) by mass spectrometry and SI, AIR, and MCRI by frequently sampled intravenous glucose tolerance tests.Elevated plasma BCAAs were inversely associated with SI and MCRI and positively associated with fasting insulin in regression models adjusted for potential confounders (β = -0.0012 [95% CI -0.0018, -0.00059], P < 0.001 for SI; β = -0.0013 [95% CI -0.0018, -0.00082], P < 0.001 for MCRI; and β = 0.0015 [95% CI 0.0008, 0.0023], P < 0.001 for fasting insulin). The association of BCAA with SI was significantly modified by ethnicity, with the association only being significant in Caucasians and Hispanics. Elevated plasma BCAAs were associated with incident diabetes in Caucasians and Hispanics (multivariable-adjusted odds ratio per 1-SD increase in plasma BCAAs: 1.67 [95% CI 1.21, 2.29], P = 0.002) but not in African Americans. Plasma BCAAs were not associated with SI-adjusted AIR.Plasma BCAAs are associated with incident diabetes and underlying metabolic abnormalities, although the associations were generally stronger in Caucasians and Hispanics.
Abstract 11824: Evidence of a Causal Relationship between Adiponectin Levels and Insulin Sensitivity: A Mendelian Randomization Study
Authors: He Gao, Tove Fall, Rob M van Dam, Allan Flyvbjerg, Björn Zethelius, Erik Ingelsson, Sara Hägg
Journal: Circulation (2012)

The adipocyte-secreted protein adiponectin has been associated with insulin sensitivity in observational studies. We aimed to evaluate whether this relationship is causal using a Mendelian randomiz...
MammoSite brachytherapy for low-risk breast carcinoma: Toxicity, cosmetic evaluation and quality-of-life results of a phase II study
Authors: Y. Belkacemi, M. Chauvet, S. Giard, S. Villette, T. Lacornerie, F. Bonodeau, M. Baranzelli, J. Bonneterre, E. Lartigau
Journal: Journal of Clinical Oncology (2007)

11016 Background: The MammoSite is a device that was developed with the goal of making breast-conserving surgery more widely available. Our objective was to evaluate the MammoSite device performances after an open cavity placement procedure and quality of life in highly selected patients with early-stage breast cancer. Methods: From March 2003 to March 2005, 43 patients with T1 breast cancer were enrolled in a phase II prospective study. Twenty-five (58%) patients were qualified for HDR brachytherapy delivery. The median age was 72 years (range: 60–75). Twenty-five (58%) were treated with high-dose rate brachytherapy using the MammoSite applicator to deliver 34 Gy prescribed at 1 cm from the balloon surface in 10 fractions over 5 to 8 days. Results: The main disqualifying factor was pathologic sentinel node involvement. After a median follow-up of 13 months, there were no local recurrences. Seventeen (68%), 13 (52%), 7 (28%), 5 (20%) and 4 (16%) patients had erythema, seroma, inflammation, hematoma and infection, respectively. Only 2 patients developed telangiectasia. At 3 months breast erythema grade ≥ 2 was significantly correlated to cosmetic results (12.5% in the ‘good to excellent‘ versus 57% in the ‘poor to fair‘ group; p = 0.045). The strongest trend of excellent cosmetic outcome was observed in patients with skin spacing ≥ 19 mm (50%) compared to patients with &lt; 19 mm (11%; p = 0.087). At 1 year the rate of ‘good to excellent‘ cosmetic results was 84%. Significant changes in QoL were observed for emotional and social well-being between 3 and 12 months. At 24 months only emotional well-being subscore changes were statistically significant (p = 0.015). Param Conclusions: To our knowledge, this is the first study since the initial FDA clinical study showing the feasibility of MammoSite brachytherapy procedure as a sole therapy in highly selected patients older than 60 years. This is also the first report on QoL during and after APBI using HDR brachytherapy with a MammoSite device. The toxicity and cosmetic results are in the range of other series. Higher range of skin spacing allowed a significant reduction of the risk of telangiectasia. QoL evaluation indicate that baseline scores were satisfactory. Changes concerned mainly emotional and social well-being. No significant financial relationships to disclose.