tbuckley/cabot-search huggingface dataset:
Reduction of Respiratory Tract Binding of Benzo[a]pyrene in Mice by Immunization2
Authors: F. Moolten, N. Capparell, E. Boger
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Reduction of Respiratory Tract Binding of Benzo[a]pyrene in Mice by Immunization Get access F. Moolten, F. Moolten 3Department of Microbiology, Boston University School of Medicine, Boston, Mass. 02118. Search for other works by this author on: Oxford Academic PubMed Google Scholar N. Capparell, N. Capparell 3Department of Microbiology, Boston University School of Medicine, Boston, Mass. 02118. Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Boger E. Boger 4Department of Chemistry, Boston College, Chestnut Hill, Mass. 02167. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 61, Issue 5, November 1978, Pages 1347–1349, https://doi.org/10.1093/jnci/61.5.1347 Published: 01 November 1978 Article history Received: 03 April 1978 Accepted: 03 July 1978 Published: 01 November 1978
Fluid phase of solid tumors, circulating tumor cells in high definition
Authors: Peter Kuhn
Journal: Clinical Cancer Research (2010)

Abstract We have established a fluid phase biopsy approach that identifies circulating tumor cells (CTCs) in the context of peripheral blood leukocytes, with no protein-based enrichment, and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. We refer to this technique as the HD-CTC assay and report on the use of this methodology to characterize the incidence of HD-CTCs in peripheral blood samples from a small cohort of metastatic cancer patients, including those with prostate cancer, breast cancer, pancreatic cancer, along with set of normal controls. Importantly, we find HD-CTC clusters ranging from 2 HD-CTCs to greater than 30 HD-CTCs in the majority of the cancer patients in this cohort. As a case study, one patient was followed over time and both cytology from a solid tumor metastasis and the HD-CTCs were quantitatively characterized. This initial validation of an enrichment-free assay demonstrates the ability to identify significant numbers of HD-CTCs in a majority of patients in prostate, breast and pancreatic cancers. Due to the enrichment free approach, the HD-CTC assay has significant implications for determining the biology of cancer spread and therapy response in both the HD-CTC population and the populations of rare events that are outside of the strict HD-CTC definition but are still fully characterized and tracked in this assay. This fluid biopsy can then be used for routine pathology evaluation and additional molecular characterization. Future studies will investigate the clinical utility of this methodology.
No “Kindlin,” it’s all about HSC balance
Authors: Paul S. Frenette
Journal: The Journal of Experimental Medicine (2015)

The Journal of Experimental MedicineAfter their inoculation by mosquitos and entry into the bloodstream, malaria sporozoites must cross the liver sinusoidal barrier to gain access to hepatocytes, where they can multiply as erythrocyte-infecting forms.In this issue, Cha et al. provide further evidence that Kupffer cells (KCs) offer a gateway for entry of sporozoites into the liver parenchyma and identify the receptor on the KCs that directs the passage of the parasite through this portal.A remarkably fruitful phage display strategy led to the identification of a peptide, P39, that bound to KCs.P39 strongly inhibited sporozoite entry into KCs in vitro and reduced liver infection in vivo.It was also shown to bind specifically to CD68, a heavily glycosylated transmembrane protein similar to LAMPs in its cellular distribution, sequence, and structure.Furthermore, the expression of CD68, at least in the liver, is confined to KCs.The function of CD68 as a receptor for sporozoite entry into KCs in vitro was supported by silencing, overexpression, and ectopic expression of the CD68 gene and by antibody inhibition.More critically, parasite liver burden in CD68 knockout mice was reduced by 71%, substantiating CD68 as a key receptor for sporozoite interaction with KCs in vivo, and KCs as the paramount gateway cells.Finally, CD68 knockout mice treated with clodronate to deplete KCs showed liver parasite burdens that were comparable to clodronate-treated, wild-type mice, which in turn had comparable infections to untreated wildtype mice.The authors conclude that CD68 serves as such an efficient gateway that sporozoite transit to the liver parenchyma proceeds as if the sinusoidal barrier did not exist.These findings still need to be reconciled with prior quantitative imaging studies that attribute a greater role for endothelial cells in sinusoid traversal and that reveal a negative impact of KCs on sporozoite survival.Beyond its function as a receptor for sporozoite entry, the nature and consequences of CD68 engagement need to be further explored.Does CD68-mediated sporozoite entry into KCs involve active penetration or phagocytosis?Is there damage to the host cell?Does CD68 engagement inhibit antigen presentation function and/or trigger release of antiinflammatory cytokines that contribute to the state of relative immune tolerance in the liver?And, crucially, what is the parasite ligand for CD68?Assuming its accessibility for antibody targeting in its native state, it would seem an ideal component of a pre-erythrocytic vaccine.
Non-Hodgkin’s lymphoma of the testis: A retrospective study of 84 patients treated in the French anticancer centres
Authors: J.-L. Lagrange, A. Ramaioli, Ch. Theodore, M.-J. Terrier-Lacombe, V. Beckendorf, P. Biron, Ch. Chevreau, P. Chinet-Charrot, J. Dumont, A. Delobel-Deroide, J. D’Anjou, C. Chassagne, R.-M. Parache, J.-M. Karsenty, J. Merrier, J.-P. Droz
Journal: Annals of Oncology (2001)
Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward
Authors: Ream Al-Hasani, Jordan G. McCall, Gunchul Shin, Adrian M. Gomez, Gavin P. Schmitz, Julio M. Bernardi, Chang-O. Pyo, Sung Il Park, Catherine M. Marcinkiewcz, Nicole A. Crowley, Michael J. Krashes, Bradford B. Lowell, Thomas L. Kash, John A. Rogers, Michael R. Bruchas
Journal: Neuron (2015)

The nucleus accumbens (NAc) and the dynorphinergic system are widely implicated in motivated behaviors. Prior studies have shown that activation of the dynorphin-kappa opioid receptor (KOR) system leads to aversive, dysphoria-like behavior. However, the endogenous sources of dynorphin in these circuits remain unknown. We investigated whether dynorphinergic neuronal firing in the NAc is sufficient to induce aversive behaviors. We found that photostimulation of dynorphinergic cells in the ventral NAc shell elicits robust conditioned and real-time aversive behavior via KOR activation, and in contrast, photostimulation of dorsal NAc shell dynorphin cells induced a KOR-mediated place preference and was positively reinforcing. These results show previously unknown discrete subregions of dynorphin-containing cells in the NAc shell that selectively drive opposing behaviors. Understanding the discrete regional specificity by which NAc dynorphinerigic cells regulate preference and aversion provides insight into motivated behaviors that are dysregulated in stress, reward, and psychiatric disease.
Impact of septoplasty in the severity and treatment of sleep apnea
Authors: Ricardo Reis, Daniela Alves, José Moutinho, Vitória Martins
Journal: European Respiratory Journal (2013)

Introduction: Current scientific evidence has yet to show significant benefit in the surgical approach of sleep apnea syndrome (SAS).

Aims: Evaluation of the impact of septoplasty in the severity and treatment of sleep apnea patients.

Methods: Revision of the patients followed in our Sleep Medicine Center who, in the period of January 1996 to December 2012, were subjected to septoplasty and performed sleep study before and after the surgical procedure.

Results: One hundred and eighty SAS patients were subjected to septoplasy and 53% (n= 96) performed sleep study before and after surgery, of which, in 51% an apnea/hypopnea or respiratory disturbance index (AHI/RDI) was calculated. Mean age was 47,8+11,1 years and 93% were male. Sleep cardiorespiratory study was performed in 71% and 86% was under CPAP treatment previously to surgery. In 51% (n=25) of the patients an amygdalectomy/adenoidectomy (A/A) or uvulopalatopharyngoplasty (UP3).

View this table:

Table 1 - Impact of Surgery on AHI/RDI





None of the types of surgery lead to significant change in AHI/RDI. After surgery 12,2% had an AHI/RDI < 5/h and 16,3% an AHI/RDI between 5 and 15/h. Surgery lead to treatment change in 24,5% of patients.

Conclusions: Septoplasty showed no significant impact in the global AHI/RDI of sleep apnea patients. However, in a minority of patients there was a change in treatment and in 12,2% sleep apnea was considered as resolved (AHI/RDI < 5/h).
NCCN Task Force Report: Molecular Markers in Leukemias and Lymphomas
Authors: Jerald P. Radich, Andrew D. Zelenetz, Wing C. Chan, Carlo M. Croce, Myron S. Czuczman, Harry P. Erba, Sandra J. Horning, Jane Houldsworth, B. Douglas Smith, David S. Snyder, Hema M. Sundar, Meir Wetzler, Jane N. Winter
Journal: Journal of the National Comprehensive Cancer Network (2009)

The introduction of targeted therapies has revolutionized treatment and improved outcomes in patients with leukemias and lymphomas. However, many patients experience relapse caused by the persistence of residual malignant cells. Cytogenetic and molecular techniques are increasingly being used to assess and quantify minimal residual disease (MRD). The emergence of advanced technologies has led to the discovery of multiple novel molecular markers that can be used to detect MRD and predict outcome in patients with leukemias and lymphomas. Gene expression signatures that predict clinical outcomes in patients with non-Hodgkin's lymphoma have been identified. In chronic myelogenous leukemia, molecular monitoring has become more important in assessing response and detecting resistance to therapy. In acute leukemias, several new markers have shown potential in prognostication and monitoring treatment. In leukemias and lymphomas, microRNAs have been identified that may be useful in diagnostics and prognostication. To address these issues, the National Comprehensive Cancer Network (NCCN) organized a task force consisting of a panel of experts in leukemia and lymphoma to discuss recent advances in the field of molecular markers and monitoring MRD.
Delayed Mortality in Sublethally Irradiated Mice Treated With Allogeneic Lymphoid and Myeloid Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Milivoj Boranić
Journal: JNCI Journal of the National Cancer Institute (1968)

RF mice were irradiated with a high sublethal dose (530 rads) of X rays and treated with C57BL spleen cells, bone marrow, or both. Administration of spleen cells produced high mortality attributable to an acute graft-vcrsus-host reaction and myeloid tissue depletion. Administration of bone marrow cells produced transient chimerism and, occasionally, midlethal dose effect. Treatment with mixed cell inocula containing 5–10 × 106 spleen cells and 30–40 × 106 bone marrow cells resulted in development of a chronic wasting syndrome terminating in death 1–2 months after treatment. In these mice, chimerism was more frequently present than in mice receiving bone marrow only. It is concluded that allogeneic immunocompetent cells may promote the take of a simultaneously administered bone marrow graft by reinforcing irradiation damage to the recipient's hematopoietic tissue. This may result in a chronic secondary disease.
Serial Cytogenetic Studies of Nonendemic Burkitt's Lymphoma Cell Lines
Authors: Edwin C. Douglass, Ian T. Magrath, Elaine C. Lee, Jacqueline Whang-Peng
Journal: JNCI Journal of the National Cancer Institute (1980)

Cytogenetic study of nonendemic Burkitt's lymphoma (BL) cell lines showed a translocation of chromosomes #8 and #14, t(8;14), present in 16 of the 18 lines examined. Serial cytogenetic studies of nine of these lines showed the t(8;14) to be stable and present in all cells examined. Although many other chromosome aberrations were present, they did not demonstrate the stability or the pervasiveness of the t(8;14). The significance of these results and previously reported cytogenetic studies on the etiology of BL was discussed.
Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Hematopoietic Growth Factor PIXY321 After Moderate-Dose Fluorouracil, Doxorubicin, and Cyclophosphamide in Stage II and III Breast Cancer
Authors: Stephen E. Jones, Pankaj Khandelwal, Kristi McIntyre, Robert Mennel, Douglas Orr, Robert Kirby, Edward Agura, Lewis Duncan, William Hyman, Tammy Roque, David Regan, Michael Schuster, Nikolay Dimitrov, Leslie Garrison, Mary Lange
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To measure the effect of PIXY321 (granulocyte-macrophage colony-stimulating factor/interleukin-3 S. cerevisiae fusion protein) on the incidence, duration, and complications of neutropenia and thrombocytopenia after moderate-dose fluorouracil 600 mg/m 2 , doxorubicin 60 mg/m 2 , and cyclophosphamide 750 mg/m 2 (FAC) chemotherapy in patients with stage II and III breast cancer. PATIENTS AND METHODS: In this multicenter, randomized, double-blind placebo-controlled trial, 71 women were to receive four 21-day cycles of treatment with moderate-dose FAC chemotherapy by short intravenous infusion on day 1, followed by either placebo or PIXY321 (375 μg/m 2 subcutaneously twice a day) on days 3 to 15. All patients were to receive prophylactic oral ciprofloxacin when the absolute neutrophil count was less than 1,000/μL. RESULTS: PIXY321 significantly reduced the incidence and duration of grade 3 and grade 4 neutropenia in cycles 1 and 2 and the duration of grade 3 neutropenia in cycles 1 through 4. In cycles 3 and 4, grade 3 thrombocytopenia was significantly more common with PIXY321 (P &lt; .05). Two patients, both in the PIXY321 group, required platelet transfusions. Fever and hospitalization for intravenous antibiotics were significantly more common in the PIXY321 group during cycle 1 only. More patients in the PIXY321 group achieved hematologic recovery by day 22 in cycles 1 through 3, and time to recovery was significantly shorter with PIXY321 in all cycles. FAC dose intensity was roughly 2% higher in the PIXY321 group (P = NS). Nonhematologic events of any intensity occurring with significantly greater overall frequency in the PIXY321 group included injection-site reactions, fever, chills, abdominal pain, and arthralgia. No patient died on study or within 30 days of her last dose of study drug. CONCLUSION: PIXY321 decreased the incidence and duration of FAC-induced grade 3 and 4 neutropenia in cycles 1 and 2 and significantly shortened the time to hematologic recovery in all cycles. However, it produced more systemic toxicity as well as thrombocytopenia in cycles 3 and 4.
Inhibition of In Vitro Growth of Lymphoma Cells by Macrophages From Tumor-Bearing Mice
Authors: Holger Kirchner, Howard T. Holden, Ronald B. Herberman
Journal: JNCI Journal of the National Cancer Institute (1975)

Spleen cells from C57BL/6 mice bearing primary tumors Induced by the Moloney strain of murine sarcoma virus (MuSV) strongly inhibited the uptake of tritiated thymidine (3H-TDR) by RBL-5 lymphoma cells in a 48-hour growthinhibition assay (GIA). This activity was first detected 7 days after MuSY was injected; it peaked at 14 days, and was usually no longer detectable after 18-21 days. It could be detected at effector cell/target cell ratios between 20: 1 and 5: 1, at which normal spleen cells had a growth-promoting effect. The effector cells in the GIA were not T cells, and various depletion experiments suggested that they were macrophages. Macrophages of a purity of over 95% were obtained in the glass-adherent fraction of thioglyconate-induced peritoneal exudate cells (PEC). PEC were growth inhibitory when obtained from either normal or MuSY tumor-bearing mice. However, at effector cell/target ratios of 2.5: 1, only PEC from MuSY tumor-b aring mice had an effect; PEC from normal mice were inactive. Activity of spleen cells in the GIA appeared distinct from T-cell-dependent specific cytotoxiCity, which was not affected by removal of macrophages. Activity in the GIA was nonspecific, and target cells which do not cross-react with RBL-5 cells were equally inhibited. Furthermore, spleen cells from mice bearing primary tumors induced by 3-methylcholanthrene were also fully active against RBL-5 cells. Supernatants from spleen cell cultures obtained from mice 14 days post injection with MuSY also inhibited the incorporation of 3H-TOR by RBL-5 cells in vitro. However, this effect seemed to be an artifact, since the tumor cells proliferated equally well in the presence or absence of the supernatants. In contrast, the direct effect of spleen cells from MuSV tumor-bearing mice was reflected both by an inhibition of cell proliferation and by inhibition of 3H-TDR incorporation.
Prognostic value of dual-time-point 18F-FDG PET in fibrotic idiopathic interstitial pneumonia
Authors: Yukihiro Umeda, Yoshiki Demura, Chisato Honjo, Yasuyuki Sumida, Miwa Morikwa, Masaki Anzai, Shingo Ameshima, Tatsuro Tsuchida, Hidehiko Okazawa, Takeshi Ishizaki, Tamotsu Ishizuka
Journal: European Respiratory Journal (2013)

Purpose : The aim of this prospective study was to clarify whether dual-time-point [18F]-2-fluoro-2-deoxy- D -glucose positron emission tomography (18F-FDG PET) imaging results are useful to predict long-term survival of idiopathic pulmonary fibrosis (IPF) and fibrotic nonspecific interstitial pneumonia (f-NSIP) patients.

Methods : Seventy patients with IPF (n=43) or f-NSIP (n=27) underwent 18F-FDG PET examinations at 2 time points; 60 minutes (early imaging) and 180 minutes (delayed imaging) after 18F-FDG injection. Standardized uptake value (SUV) at each point and the retention index value (RI-SUV) calculated from those were evaluated, then the results were compared with survival and serial trends in pulmonary function indices.

Results : The early SUV value for lung lesions in patients with f-NSIP (1.31±0.45) was significantly higher than that in those with IPF (1.09±0.31, P =0.014), whereas the delayed SUV and RI-SUV values were not significantly different. There was no significant difference in survival between the patients groups ( P =0.24). The 3-year survival of all patients (IPF and f-NSIP) negative for RI-SUV (<0%) was 96.7% as compared to 50.8% for those with positive RI-SUV (≥0%; P <0.0001). Positive RI-SUV was shown to be a robust predictor of survival in both groups (IPF, HR 4.67, 95% CI 1.23-17.8, P =0.023; f-NSIP, HR 8.88, 95% CI 1.04-75.9, P =0.046) when compared with baseline FVC, DLCO, and pathological diagnosis.

Conclusion : Our results demonstrate that positive RI-SUV is strongly predictive of long-term survival and changes in pulmonary function in patients with IPF or f-NSIP.
Abstract 13062: Life's Simple 7 in 2003-2007 and Mortality in Blacks and Whites: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort
Authors: Mary Cushman, Suzanne E Judd, Virginia J Howard, Neil A Zakai, Brett Kissela, Dawn Kleindorfer, Monika M Safford, George Howard
Journal: Circulation (2010)
RUNX2 and the PI3K/AKT axis reciprocal activation as a driving force for tumor progression
Authors: Karine A. Cohen-Solal, Rajeev K. Boregowda, Ahmed Lasfar
Journal: Molecular Cancer (2015)

From the first reported role of the transcription factor RUNX2 in osteoblast and chondrocyte differentiation and migration to its involvement in promigratory/proinvasive behavior of breast, prostate, and thyroid cancer cells, osteosarcoma, or melanoma cells, RUNX2 currently emerges as a key player in metastasis. In this review, we address the interaction of RUNX2 with the PI3K/AKT signaling pathway, one of the critical axes controlling cancer growth and metastasis. AKT, either by directly phosphorylating/activating RUNX2 or phosphorylating/inactivating regulators of RUNX2 stability or activity, contributes to RUNX2 transcriptional activity. Reciprocally, the activation of the PI3K/AKT pathway by RUNX2 regulation of its different components has been described in non-transformed and transformed cells. This mutual activation in the context of cancer cells exhibiting constitutive AKT activation and high levels of RUNX2 might constitute a major driving force in tumor progression and aggressiveness.
Abstract 11337: Acute Reduction In Mechanical Dyssynchrony by Speckle Tracking Strain After Cardiac Resynchronization Therapy is Assocated with Long Term Outcome
Authors: Olusegun A Oyenuga, Tetsuari Onishi, Toshinari Onishi, Stephanie C Haberman, Evan Adelstein, Samir Saba, John Gorcsan
Journal: Circulation (2011)

Background: Response to cardiac resynchronization therapy (CRT) remains variable. Baseline mechanical dyssynchrony has been associated with left ventricular (LV) reverse remodeling and long term survival, however, the significance of acute mechanical resynchronization is unclear. Methods: We hypothesized that a significant reduction in degree of dyssynchrony immediately after CRT is associated with acute LV remodeling and favorable long term outcome. We studied 103 consecutive CRT patients: NYHA Class III-IV, ejection fraction (EF) ≤ 35%, and QRS ≥120ms. Echocardiographic examination was performed on all patients prior to CRT and 1±1 day after CRT. EF was calculated using Simpson's biplane method. Radial dyssynchrony was assessed in the mid-LV short axis view. Long term outcome events were pre-specified as death, transplant or left ventricular assist device (LVAD) over 4 years after CRT. Results: Follow up echo data and dyssynchrony determination was feasible in 85 patients (83%). The study group's age wa...
Late-breaking abstract: Olodaterol inhibits pro-fibrotic mechanisms in primary human lung fibroblasts
Authors: Franziska Herrmann, Lutz Wollin, Eva Wex
Journal: European Respiratory Journal (2014)

Background:  Pro-fibrotic activity of lung fibroblasts results in airway remodeling observed in COPD. β2-agonists were shown to inhibit fibrotic events including fibroblast proliferation and extracellular matrix synthesis. However, these effects were mainly shown in cell lines but not in primary human lung fibroblasts.   Aim:  To test the efficacy of the long-acting β2-agonist (LABA) olodaterol to inhibit pro-fibrotic events in primary human lung fibroblasts (HLFs).   Methods:  HLFs were pre-treated with olodaterol for 30 min and subsequently stimulated with pro-fibrotic mediators (TGF-β, PDGF, FGF) in the presence of olodaterol. Transformation, migration or proliferation assays were performed for 48, 72 or 90 h, respectively. Alpha-smooth muscle actin (α-SMA) expression was measured by FACS analysis, proliferation was determined by BrdU incorporation and cell motility was determined by time lapse microscopy and manual single cell tracking.   Results:  Functionality of the β2-receptor on HLFs was determined measuring olodaterol-induced cAMP release. Olodaterol concentration-dependently induced cAMP with an IC 50  of 200 pM. Stimulation of primary HLFs with TGF-β-induced α-SMA expression and stimulation with both, PDGF and FGF, induced fibroblast proliferation and motility. TGF-β-induced α-SMA expression was attenuated by olodaterol with an IC 50  value of 10 pM and a maximal efficacy of 90 % at 300 pM. With similar IC 50  values olodaterol also reduced PDGF- or FGF-induced proliferation (∼50 and 30% at 1 nM) and motility (∼45 and 85% at 1 nM).   Conclusions:  Olodaterol attenuates pro-fibrotic events in primary human lung fibroblasts. These data support additional beneficial functions of olodaterol beyond bronchodilation.