tbuckley/cabot-search huggingface dataset:
Abstract 3585: Metastasis of 4T1 murine breast cancer cells to the lung is dependent on the chemokine CCL2/MCP-1 produced by stromal cells in the primary tumor
Authors: Teizo Yoshimura, O.M. Zack Howard, Toshihiro Ito, Masaki Kuwabara, Akihiro Matsukawa, Keqiang Chen, Ying Liu, Mingyong Liu, Ji Ming Wang
Journal: Cancer Research (2014)

Abstract The chemokine CCL2, also known as MCP-1, plays an important role in the initiation and progression of cancer. Since tumor cells produce CCL2, they are considered to be the main source of this chemokine. Here, we examined the capacity of CCL2 produced by non-tumor cells to affect the growth and lung metastasis of 4T1 mouse breast cancer cells. Primary tumors formed in the mammary pad of WT or CCL2-/- mice grew at a similar rate; however, lung metastases were markedly reduced in CCL2-/- mice, with significantly longer mouse survival. High levels of CCL2 mRNA were detected in tumors growing in WT, but not CCL2-/- mice. Serum CCL2 levels were increased in tumor-bearing WT, but not CCL2-/- mice. Transplantation of CCL2-/- bone marrow cells into WT mice did not alter the incidence of lung metastasis, but transplantation of WT bone marrow cells into CCL2-/- mice increased lung metastasis. The primary tumors of CCL2-/- mice consistently developed necrosis earlier than those of WT mice and showed decreased infiltration by macrophages and reduced angiogenesis. Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of CCL2. Intravenous injection of 4T1 cells producing a high level of CCL2 resulted in increased tumor foci in the lung of CCL2-/- mice. Finally, the culture supernatants of 4T1 cells markedly induced CCL2 production in mouse macrophages. Thus, CCL2 produced by tumor cell-activated stromal cells in the primary tumors promotes lung metastasis of 4T1 cells, while tumor cell-derived CCL2 also contributes to the metastasis once tumor cells enter the circulation. A greater understanding of the source and role of CCL2 during tumor progression and the mechanisms by which stromal cells produce this chemokine may lead to novel strategies for cancer treatment. Citation Format: Teizo Yoshimura, O.M. Zack Howard, Toshihiro Ito, Masaki Kuwabara, Akihiro Matsukawa, Keqiang Chen, Ying Liu, Mingyong Liu, Ji Ming Wang. Metastasis of 4T1 murine breast cancer cells to the lung is dependent on the chemokine CCL2/MCP-1 produced by stromal cells in the primary tumor. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3585. doi:10.1158/1538-7445.AM2014-3585
Poly(ethylene carbonate)s, part II11Part I: see Ref. [15].: degradation mechanisms and parenteral delivery of bioactive agents
Authors: Georg H Stoll, Fritz Nimmerfall, Murat Acemoglu, David Bodmer, Siegfried Bantle, Irene Müller, Andreas Mahl, Maryelle Kolopp, Kjell Tullberg
Journal: Journal of Controlled Release (2001)
975. TSTA Mediated Multi-Modality Gene-Expression Imaging in Hormone Refractory Prostate Cancer
Authors: Makoto Sato, Mai Johnson, Liqun Zhang, Sanjiv S. Gambhir, Michael Carey, Lily Wu
Journal: Molecular Therapy (2004)

Currently no effective treatment is available for metastatic hormone refractory prostate cancer (HRPC). Hence, gene therapy represents a promising therapeutic strategy for such disease. In an attempt to develop an efficient and safe protocol to treat HRPC, we generated a highly augmented prostate specific two-step transcriptional amplification (TSTA) system to mediate targeted gene expression. Adenoviral vectors carrying the TSTA system (AdTSTA) exhibits activities that exceeds the CMV promoter while maintaining prostate specificity and androgen regulation in vivo (Sato et al. Mol Ther 2003, 8:726). The TSTA system consists of: 1) the GAL4-VP16 potent activator regulated by a modified PSA promoter/enhancer, and 2) a GAL4 responsive promoter driven transgene. TSTA activity critically relies on androgen receptor (AR) function. In this study, we aimed to determine the activity of AdTSTA in HRPC models such that future TSTA-based diagnostic and therapeutic applications can be utilized in this advanced disease.
Phase II trial of oxaliplatin (OXA) combined with paclitaxel (P) inplatinum + taxanes sensitive advanced ovarian cancer (AOC) patients: Final results
Authors: P. Viens, T. Petit, A. Yovine, P. Bougnoux, G. Deplanque, P. Cottu, R. Delva, J. P. Lotz, J. S. Van Belle, J. M. Extra
Journal: Journal of Clinical Oncology (2004)

5023 Background: OXA is active in mismatch repair (MMR) deficient cells, a condition prevalent in pretreated AOC. OXA/P shows high activity in investigator initiated studies (Faivre et al, Ann Oncol 10:1125, 1999). We evaluated efficacy and safety of OXA/P in AOC pts with clinically evaluable disease pretreated with 1 platinum based regimen ± taxanes and a progression-platinum-free interval (PPFI) ≥6 months (mo). Methods: From Dec 99 to Apr 02, 105 pts, 14 centres received P 175 mg/m2, 3h iv followed by OXA 130 mg/m2, 2h iv, every 3 weeks, for up to 9 cycles (cy) without G-CSF. Median (m) age: 58 years (range 37–83), 96% PS 0/1. PPFI: 69 pts >12 mo, 34 pts 6–12 mo; 80 pts (76%) taxane-pretreated. Results: 708 cy administered; m 7 cy/pt (1–9). Relative dose intensity: OXA 0.95, P 0.97. Efficacy: 98 pts eligible, 7 non-eligible (3 bowel occlusion, 3 >1 prior platinum-based chemotherapy, 2 PPFI not determinable). 98 pts evaluable for response (see table) ORR: 81% (95%CI 71–88), all but 3 responses third party reviewed; 90 pts evaluable for biological response (baseline CA125 ≥50 UI/ml): 89% response (decrease >75% or CA125 normalization >1 mo). Combined RECIST /biological response: 88% (95%CI 80–94). M follow-up: 27 mo (14–48); m PFS: 10.2 mo; projected OS >28 mo (44 events). Safety (NCI-CTC); % pts with grade (gr) 3/4: neutropenia 21/46; thrombocytopenia 15/1; nausea-vomiting 9/2; asthenia 7/1; allergic reaction: 1/1; cumulative reversible neurotoxicity gr 2/3 (OXA specific scale): 50/25 after a m 7 cy (3–9); febrile neutropenia: 9 episodes/8 pts; 4% cy required G-CSF; no treatment-related deaths. Conclusion: The OXA/P combination shows the highest level of efficacy in platinum-sensitive third party reviewed large phase II studies in platinum/taxane pretreated AOC pts with PPFI >6 mo, and can be administered in an outpatient setting without special safety measures. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MGI Pharma, Inc.
Critics Bash HIV Vaccine Trial Analysis
Authors: Mike Mitka
Journal: JAMA (2003)

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
The role of Abcg2 expression in hematopoietic stem cells
Authors: Brian Sorrentino
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

SY31-2 

The Side Population (SP) assay is used for the enrichment of hematopoietic stem cells (HSCs), however this assay is not specific for HSCs and causes toxicity when cells are exposed to Hoechst dye. The SP phenotype has been associated with expression of the Abcg2 transporter, which is expressed in HSCs and mediates Hoechst dye efflux. To explore the functional effects of Abcg2 expression in HSCs, we have generated Abcg2 knockout mice and shown that Abcg2 null HSCs are dramatically sensitized to mitoxantrone, suggesting that the function of Abcg2 in HSCs is to protect from naturally occurring toxic substrates and mutagens. These data have relevance to AML, where malignant HSCs may co-opt resistance mechanisms present in normal HSCs. In our most recent work, we have asked whether expression of Abcg2 would allow for prospective isolation of HSCs. Mice were generated with a GFP reporter gene inserted into the Abcg2 locus. Bone marrow cells that expressed GFP and lacked expression of lineage-specific markers (Lin-) were isolated by flow cytometry and tested for HSC activity. Irradiated recipient mice were reconstituted with as little as 10 cells, while as many as 60,000 Lin-, GFP- cells gave no reconstitution. Secondary transplant studies confirmed that the Lin-, GFP+ cells were indeed long term repopulating, self-renewing HSCs. These results show that essentially all murine HSCs express Abcg2, and that Abcg2 expression provides a new and simple purification strategy for HSCs. Furthermore, we have identified populations of Abcg2-expressing cells in the skeletal muscle that may represent non-hematopoietic stem cells.
Abstract 15927: Successful Pharmacological Cardioversion by Oral Amiodarone Therapy is Correlated With Favorable Post-Ablation Clinical Outcomes in Non-Paroxysmal Atrial Fibrillation
Authors: Kiyoshi Otomo, Kaname Takizawa, Naoto Inoue, Taiichiro Meguro
Journal: Circulation (2014)

Backgrounds: Catheter ablation (CA) for non-paroxysmal atrial fibrillation (AF)(non-PAF) is less successful in patients (pts) with highly remodeled atria. It is still controversial that how far CA should be indicated in non-PAF pts with highly remodeled atria. Impacts of successful pharmacological cardioversion of non-PAF by oral amiodarone (AMD) on post-CA clinical outcomes remain to be evaluated. Purposes: To assess efficacy of oral AMD and implications of successful cardioversion by AMD in advance to CA on post-CA clinical outcomes in non-PAF pts. Methods: In consecutive 418 non-PAF pts (age: 63±9 years, AF duration: 28±37 months, LA diameter: 44±5mm), oral AMD (300 mg/day for 2 weeks and 100 mg/day thereafter) was initiated at outpatient clinic one month prior to the initial CA procedure. Recurrence-free survival after last CA procedure was compared between those with successful pharmacological conversion to sinus rhythm, atrial flutter or atrial tachycardia by the time of the initial CA procedure (Group non-AF) and those without (Group AF) . Results: At the beginning of initial CA procedure, 79 pts were in sinus rhythm, 8 in typical atrial flutter, 3 in atrial tachycardia (Group non-AF: 90 pts (22%)) and the remaining 328 still in AF (Group AF: 78%) . During follow-up period of 287±204 days after last CA procedure (procedure number:1.6±0.7/pt, range: 1-4), 45 pts (11%) were followed up while taking AMD, whereas the other 373 pts (89%) without any antiarrhythmic drugs. Kaplan-Meier analysis revealed that recurrence-free survival after last CA procedure was significantly higher in Group non-AF than in Group AF (88 (98%) vs. 291 (89%) pts; p=0.02) . Group non-AF pts exhibited significantly shorter AF duration (9±9 (range: 1-46) vs. 33±41 months (range: 1-240): p&lt;0.0001) and smaller LA diameter (42±5 (range: 28-54) vs. 44±5 mm (range: 31-61): p&lt;0.0001) as compared with those in Group AF pts. Conclusions: Successful cardioversion by AMD in advance to CA was correlated with higher recurrence-free survival after last CA procedure. This simple criterion is helpful to find pts with less remodeled atria and good candidates for CA who will benefit from CA in non-PAF pts.
Paraoxonase 1 (PON1) 55 polymorphism, lipid profiles and psoriasis
Authors: M. Asefi, A. Vaisi‐Raygani, F. Bahrehmand, A. Kiani, Z. Rahimi, H. Nomani, A. Ebrahimi, H. Tavilani, T. Pourmotabbed
Journal: British Journal of Dermatology (2012)

Paraoxonase 1 (PON1) is a serum high-density lipoprotein-bound enzyme with antioxidant function. It hydrolyses lipid peroxides, protecting low-density lipoproteins from oxidative modifications. Patients with psoriasis are at greater risk of oxidative stress, which is associated with abnormal plasma lipid metabolism.In this study, association of the PON1 55 M allele with serum arylesterase (ARE) activity, malondialdehyde (MDA), lipid profiles and psoriasis was investigated.The present case-control study consisted of 100 patients with psoriasis with and without cardiovascular diseases (mean age 35·3 years) and 100 sex- and age-matched unrelated healthy controls (mean age 35·7 years) from the population of western Iran. The PON1 55 Met>Leu polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism. Serum ARE activity, MDA, and lipid and apolipoprotein levels were determined spectrophotometrically, by high-performance liquid chromatography and by enzyme assay, respectively.The presence of the PON1 55 M allele was found to be associated with psoriasis (odds ratio = 1·96, P = 0·017). The patients with psoriasis with the PON1 M (M/L + M/M) allele had higher MDA levels (4·12 ± 0·88 vs. 2·24 ± 0·55 μmol L(-1) , P < 0·001), apolipoprotein B (APOB)/APOA1 ratio (0·91 ± 0·66 vs. 0·66 ± 0·35, P = 0·004), APOB (111 ± 38·7 vs. 88·3 ± 22·5 mg mL(-1) , P = 0·001) and lipoprotein(a) [LP(a)] (21·9 ± 18·4 vs. 15·8 ± 16·6 mg mL(-1) , P = 0·034), but lower ARE activity (39·6 ± 11 vs. 45·9 ± 11·8 U mL(-1) , P = 0·031) than the control subjects. ARE activity showed a significant positive correlation with APOA1 and a negative correlation with MDA concentration in patients with psoriasis.The PON1 55 M allele is a risk factor for psoriasis. Carriers of this allele have high levels of MDA, APOB and LP(a), a high APOB/APOA1 ratio and low ARE activity. These results indicate that oxidative stress, impairment of the antioxidant system and abnormal lipid metabolism may play a role in the pathogenesis and progression of psoriasis and its related complications. These data suggest that patients with psoriasis are more susceptible to vascular diseases.
616. Retargeted Selectively Replicating Adenoviruses for the Therapy of Colon Cancer
Authors: Krisztian Gy Homicsko, Christophe Fuerer, Richard Iggo
Journal: Molecular Therapy (2004)

In virtually all colon cancer cell lines b-catenin is activated. The target genes of b-catenin are activated through interaction of b-catenin with the transcription factor TCF. Previously in our laboratory conditionally replicating adenoviruses with TCF binding sites in the early viral promoters were constructed. We inserted TCF sites into the E1A, E1B and E4 early promoters of the wild type adenovirus. This virus, vKH1, shows 1000-fold selectivity for colon cancer cells compared to wild type Ad5.
Abstract 262: Identification Of Novel Therapeutic Targets For Catecholaminergic Polymorphic Ventricular Tachycardias In A Knock-in Mouse Model With Ryanodine Receptor Mutation R4496C.
Authors: Barbara Colombi, Nian Liu, Fausto Feletti, Carlo Napolitano, Silvia Priori
Journal: Circulation (2007)

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a disease caused by mutations in the RYR2 gene encoding the cardiac ryanodine receptor and characterized by adrenergically mediated polymorphic VT. Triggered activity (TA) mediated delayed afterdepolarizations (DADs) are considered the arrhythmogenic mechanism of CPVT. Since DADs/TA develop during intracellular calcium overload and at fast heart rate we tested 4 compounds acting on targets that are critical for calcium homeostasis [L-type Ca ++  Channel blocker Verapamil (VER); Na + -Ca ++  exchanger blocker (NCX) SEA0400 (SEA); RyR2 blocker Tetracaine (TETR)]; or implicated in heart rate control Ivabradine (IVA). TA was induced in 67% ventricular myocytes (n=15) isolated from heterozygous (He) mice R4496C  exposed to Caffeine (Caf, 300μmol/L) and Epinephrine (Epi, 200nmol/L) but in none of the wild type myocytes (n=12). 50μM TETR, 10μM SEA and 10μM VER completely abolished TA in myocytes from He-mice R4496C : lower dosages of all drugs failed to abolish TA. IVA 10μM did not prevent TA in paced myocytes from He-mice R4496C . Administration of Caf (120mg/kg) and Epi (2mg/kg) in vivo induced VT in 15/31 (48%) He-mice R4496C : occurrence of VT was unchanged by chronic (5 days intraperitoneal) administration of TETR and SEA. Conversely, VERA (40mg/kg/day) prevented VT. Interestingly IVA (5mg/kg/d) had a powerful protective effect (VT= 1/12, P  targeting NCX or RYR2 with blocking drugs abolishes TA in vitro but is not effective in preventing arrhythmias in vivo.  Blockade of L-type calcium channels prevents TA in vitro and VT in vivo.  Lowering heart rate by blocking If current with IVA prevents arrhythmias in vivo; the lack of efficacy of IVA in paced myocytes support the view that its antiarrhythmic action is played by the reduction of rate.
174. High Efficiency HDAd-Mediated Hepatic Transduction Can Be Achieved by Delivery into the Surgically Isolated Liver of Nonhuman Primates
Authors: Eduard Ayuso, Miguel Chillon, Felix Garcia, Judith Agudo, Anna Andaluz, Virginia Haurigot, Assumpcio Bosch, Pedro J. Otaegui, Fatima Bosch
Journal: Molecular Therapy (2004)

Type 1 diabetes results from autoimmune destruction of pancreatic β cells. This process might be reverted by genetically engineering endocrine pancreas in vivo to express factors that induce β-cell replication and neogenesis and counteract the immune response. However, the pancreas is difficult to manipulate and pancreatitis is a serious concern, which has made effective gene transfer to this organ elusive. Thus, new approaches for gene delivery to pancreas in vivo are required. Here we show that mouse pancreatic β-cells were efficiently transduced, and they expressed β-galactosidase after systemic injection of adenovirus with clamped hepatic circulation. Seven days after vector administration about 70% of pancreatic islets showed β-gal expression. In these islets, about 20% of the β-cells were transduced by the adenoviruses. Furthermore, scattered acinar cells expressing β-gal were also observed. In addition to mouse, we also examined the ability of adenovirus to transduce dog pancreas. We have observed that acinar, ductal and endocrine pancreatic cells were transduced after injection of adenovirus in dogs underwent local clamping of pancreatic circulation. Thus, these approaches may be used to transfer genes of interest to pancreas for both the study of islet biology and the gene therapy of diabetes and other pancreatic disorders.
Kenneth M. Brinkhous, MD
Authors: William W. McLendon
Journal: JAMA (2001)

and renowned coagulation researcher, died at his home in Chapel Hill on December 11, 2000, at the age of 92.A native of Iowa, Brinkhous received the MD degree from the University of Iowa in 1932 and remained on the faculty there until World War II.From 1946 to 1973 he was chair of the pathology department at the University of North Carolina at Chapel Hill, where he built a department noted for its balanced excellence in teaching, clinical services, and research.Working in a building named for him that towered over the campus, he remained active in research until several years before his death.He was recognized in the 1990s as the only researcher to have been funded continuously by the National Institutes of Health (NIH) for 50 years.Like others of his generation, Brinkhous was a product both the Great Depression and World War II.He personally lived frugally and spent the research funding entrusted to him with the same care.In lectures to students regarding the link between economics and disease, he explained that his interest in the stock market resulted from his observation that the 1929 stock market crash was a leading cause of death and deserved serious study as any other disease.In World War II he served as a lieutenant colonel in the Army Medical Corps commanding an army field laboratory in the South Pacific.Dealing with military personnel, shortages, and red tape prepared him well for dealing with university and NIH bureaucracies.He always approached administrative obstacles as challenges that should be addressed with the same analysis and en-
Abstract 15229: High Standardized Uptake Value of 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography was correlated with Disease Activity in Patients with Takayasu Arteritis
Authors: Daisuke Tezuka, Go Haraguchi, Takashi Ishihara, Hiroshi Inagaki, Shigeki Kimura, Shunji Yoshikawa, Kouji Higuchi, Mihoko Kawabata, Hitoshi Hachiya, Kenzo Hirao, Jun-ichi Suzuki, Mitsuaki Isobe
Journal: Circulation (2010)

Introduction: The clinical value of 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) in diagnosis of Takayasu Arteritis (T.A) has not been decided. Clinical eval...
La Manne-Porte, Etretat
Authors: M Therese Southgate
Journal: JAMA (2005)

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