tbuckley/cabot-search huggingface dataset:
Effects of Tumor Promoters and Steroidal Anti-inflammatory Agents on Skin of Newborn Mice In Vivo and In Vitro2
Authors: T. J. Siaga, U. Lichti, H. Hennings, K. Elgjo, S. H. Yuspa
Journal: JNCI Journal of the National Cancer Institute (1978)

The phorbol esters 12-O-tetradecanoylphorbol-13- acetate (TPA) and 12-O-hexadecanoylphorbol-13 acetate (HPA) are not only potent tumor promoters but also potent stimulators of epidermal DNA synthesis and ornithine decarboxylase (ODC) activity in adult mice. However, when applied topically to newborn mice, TPA and HPA have essentially no effect on epidermal and dermal DNA synthesis or on epidermal ODC activity. Exposure of primary cultures of newborn mouse epidermal cells to TPA or HPA markedly stimulated both DNA synthesis and ODC activity. The anti-inflammatory steroids dexamethasone and fluocinolone acetonide (FA) were found to be potent inhibitors of tumor promotion and epidermal DNA synthesis in adult mice. However, when applied topically to newborn mice, FA did not inhibit epidermal or dermal DNA synthesis but stimulated it approximately twofold at 48 hours after FA treatment. In primary cultures of epidermal cells from newborn mice, treatment with dexamethasone or FA caused an early stimulation of DNA synthesis followed by a 50% inhibition of DNA synthesis 2–3 days after a 1-hour pulse treatment. Also, DNA synthesis was moderately inhibited when FA was added to primary cultures of dermal fibroblasts. In their reaction to tumor promoters, epidermal cells in culture behaved more like adult than newborn mouse epidermis in vivo, whereas anti-inflammatory steroids gave an intermediate response.
Susceptibility of Mammary-Tumor-Virus-Free BALB/c Mouse Mammary Nodule Outgrowth Cells in DNA Synthesis to 3-Methylcholanthrene Tumorigenesis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Richard Adamson, M. R. Banerjee, Daniel Medina
Journal: JNCI Journal of the National Cancer Institute (1971)

DNA synthesis and its relationship to tumorigenic potential of 3-methylcholanthrene (MCA) were studied in mammary-tumor-virus-free D1 hyperplastic alveolar mammary nodule outgrowths of BALB/c mice. As measured by 3H-thymidine (3H-TDR) radioactivity in an acid-insoluble fraction, DNA synthesis in the outgrowths, after an initial slow increase, rose to a peak at 4 weeks and then declined between 1 and 8 weeks after fat-pad transplantation. Similarly, the frequency of 3H-TDR-labeled alveolar cells measured by autoradiography also increased sharply, reached a peak at 4 weeks, and then declined. Measurement of the percentage of fat pad filled by the outgrowth at different weeks indicated that the tissue did not grow exponentially but the proliferative rate was more rapid during the initial weeks followed by periods of less active growth. Administration of MCA to host mice at 3 and 5 weeks after transplantation produced over 61 % mammary tumors in the outgrowth, whereas the same treatment given between 9 and 11 weeks led to only 26% tumor incidence. These results strongly indicate that the higher incidence of mammary tumors in D1 nodule outgrowth corresponds with the period of increased DNA synthesis in the tissue at the time of carcinogen treatment. Thus, it is suggested that the cells in DNA synthesis are more susceptible to the tumorigenic action of MCA.
Neoplasms Following Childhood Radium Irradiation of the Nasopharynx&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Dale P. Sandler, George W. Comstock, Genevieve M. Matanoski
Journal: JNCI Journal of the National Cancer Institute (1982)

Eighteen to 35 years after admission to a clinic for the prevention of deafness, no increased overall cancer risk could be detected among 904 persons who had been treated with nasopharyngeal radium irradiation when compared with the risk among 2,021 persons who were either treated surgically or not treated at all, although there were differences at specific sites. An increased risk of developing both benign and malignant head and neck tumors was found among irradiated persons. Whereas no one head and neck site showed a statistically significant excess, a slight excess of brain cancer occurred 15-20 years after radium treatment. No increase in thyroid cancer risk was observed, a result possibly attributable to the low radiation doses to this organ, and the relatively small population irradiated.
Selective Inhibition by Kanamycin of Focus Formation by Rous and Moloney Sarcoma Viruses2
Authors: W. H. Murphy, J. Maisel, C. Bullis, A. J. Faras
Journal: JNCI Journal of the National Cancer Institute (1974)

Kanamycin at a concentration of 500 µg/ml inhibited focus formation by the Bryan and Schmidt-Ruppin strains of Rous sarcoma virus (RSV) about 90 and 70%, respectively. At a dose of 400 µg/ml it suppressed focus formation by Moloney sarcoma virus (MSV) about 65%. Aminodeoxykanamycin (ADK) at 100–200 µg/ml completely prevented the appearance of RSV foci and decreased MSV foci 50–75%. The drug was not toxic to cells or directly virucidal. It only slightly repressed virus attachment, penetration, eclipse, and replication. At concentrations that prevented focus formation, ADK did not inhibit RSV RNA-directed DNA polymerase. Tumor formation in vivo by MSV or RSV was not altered significantly by kanamycin or ADK.
Chemotherapy in malignant pleural mesothelioma. A review.
Authors: S T Ong, N J Vogelzang
Journal: Journal of Clinical Oncology (1996)

PURPOSE AND DESIGN We reviewed the published literature of clinical studies in malignant pleural mesothelioma, including phase II trials of the newer antifolates and plant derivatives, as well as older single-agent and combination chemotherapy trials. We excluded trials with less than 15 patients, although we have mentioned smaller trials in the text to make a specific point, as well as ones that show promise. We have also included confidence intervals when cited in the original reports, or calculated them when absent. RESULTS No drugs have consistently induced a response greater than 20%. Higher response rates have been reported with detorubicin, high-dose methotrexate, and edatrexate at 26%, 37%, and 25%, respectively, but these have yet to be confirmed. Agents that produce response rates in 10% to 20% of patients include doxorubicin, epirubicin, mitomycin, cyclophosphamide, ifosfamide, cisplatin, and carboplatin. Combination chemotherapy trials do not demonstrate a consistently greater response rate than single-agent trials. However, the combination of doxorubicin, cisplatin, bleomycin, and mitomycin demonstrated a response rate of 44% (95% confidence interval, 27% to 63%), but this remains unconfirmed. Intrapleural therapy using interferon gamma, particularly for small-volume disease, shows promise. CONCLUSION The successful treatment of unresectable pleural mesothelioma awaits the discovery of active drugs. Recent trials of high-dose methotrexate and other antifolates are encouraging. Newer agents, including suramin, should be evaluated in phase II trials. Off-protocol combination therapy cannot be recommended over single-agent therapy, but studies that use combinations of the newer agents should be conducted.
The double challenge of resistant hypertension and chronic kidney disease
Authors: Patrick Rossignol, Ziad A Massy, Michel Azizi, George Bakris, Eberhard Ritz, Adrian Covic, David Goldsmith, Gunnar H Heine, Kitty J Jager, Mehmet Kanbay, Francesca Mallamaci, Alberto Ortiz, Raymond Vanholder, Andrzej Wiecek, Carmine Zoccali, Gérard Michel London, Bénédicte Stengel, Denis Fouque
Journal: The Lancet (2015)
NUP160–SLC43A3 Is a Novel Recurrent Fusion Oncogene in Angiosarcoma
Authors: Naoki Shimozono, Masatoshi Jinnin, Mamiko Masuzawa, Mikio Masuzawa, Zhongzhi Wang, Ayaka Hirano, Yukiko Tomizawa, Tomomi Etoh-Kira, Ikko Kajihara, Miho Harada, Satoshi Fukushima, Hironobu Ihn
Journal: Cancer Research (2015)

Angiosarcoma is a malignant vascular tumor originating from endothelial cells of blood vessels or lymphatic vessels. The specific driver mutations in angiosarcoma remain unknown. In this study, we investigated this issue by transcriptome sequencing of patient-derived angiosarcoma cells (ISO-HAS), identifying a novel fusion gene NUP160-SLC43A3 found to be expressed in 9 of 25 human angiosarcoma specimens that were examined. In tumors harboring the fusion gene, the duration between the onset of symptoms and the first hospital visit was significantly shorter, suggesting more rapid tumor progression. Stable expression of the fusion gene in nontransformed human dermal microvascular endothelial cells elicited a gene-expression pattern mimicking ISO-HAS cells and increased cell proliferation, an effect traced in part to NUP160 truncation. Conversely, RNAi-mediated attenuation of NUP160 in ISO-HAS cells decreased cell number. Confirming the oncogenic effects of the fusion protein, subcutaneous implantation of NUP160-SLC43A3-expressing fibroblasts induced tumors resembling human angiosarcoma. Collectively, our findings advance knowledge concerning the genetic causes of angiosarcoma, with potential implications for new diagnostic and therapeutic approaches.
Effect of Alcohol on Social Phobic Anxiety
Authors: Joseph A. Himle, James L. Abelson, Hedieh Haghightgou, Elizabeth M. Hill, Randolph M. Nesse, George C. Curtis
Journal: American Journal of Psychiatry (1999)

Previous research has demonstrated a greater-than-expected association between social phobia and alcohol use disorders. The purpose of this study was to test the hypothesis that drinking alcohol reduces social phobic anxiety.Treatment-seeking individuals with social phobia (N = 40) were asked to give two impromptu speeches. Twenty subjects received a placebo alcoholic drink before both speeches, and 20 subjects received a placebo before the first speech, followed by a moderate dose of alcohol before the second speech. Subjective anxiety ratings, heart rate, and cognitions related to social anxiety were used as measures of anxiety.Repeated measures analyses of variance yielded no significant differences in anxiety (subjective, physiological, cognitive) between the alcohol and placebo groups. Current and past drinking habits did not significantly alter the effect of alcohol on anxiety. The belief that one received alcohol was significantly related to levels of subjective anxiety and negative cognitions.Alcohol does not directly reduce social phobic anxiety. The belief that one received alcohol may reduce social anxiety.
Serum Requirements for In Vivo Modulation of Thymus-Leukemia Antigens on Mouse Leukemia Cells and Thymocytes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Christopher W. Stackpole
Journal: JNCI Journal of the National Cancer Institute (1979)

Mouse leukemia cells and normal thymocytes bearing thymus-leukemia (TL) cell surface antigens were previously shown to acquire resistance to lysis by guinea pig complement (C) during incubation with TL alloantiserum in vitro at 37° C due to heat-labile serum activity resulting in deposition of mouse C3 onto the cell surface. The role of heat-labile serum activity and C3 in modulation of TL+ cells in vivo in mice actively or passively immunized against TL antigens was investigated. Mice of the TL-/TL+ C57BL/6J (B6) strain and the B6 congenic strain B6-Tlaa possessed poorly modulating sera, and the radiation-induced A-strain leukemia RADA1 transplanted Into B6 mice passively Immunized with heated (56° C) TL antiserum failed to modulate; thymocytes of B6-Tlaa mice Immunized similarly also did not modulate. A specific requirement for mouse C3 deposition onto RADA1 cells to achieve a modulated state was demonstrated in actively immunized TL- (B6 × A-Tlab)F1 mice in which circulating C3 and modulating activity were depleted by administration of cobra venom factor. In immunized (B6 × A-Tlab)F1 mice bearing RADA1 transplants and repeatedly given injections of B6 serum, tumor cells escaped immune destruction despite a lack of modulation. Thus modulation of TL antigenicity on tumor cells in vivo, but not tumor escape, required cell-bound C3.
Clinical Surveillance After Feeding Oral Attenuated Live Polio Vaccine
Authors: H N Macdonald, C E van Rooyen
Journal: JAMA (1963)

During widespread administration of oral poliomyelitis vaccine in the United States and Canada, a number of neurological conditions occurring within 30 days of vaccine administration were reported. After careful investigation, 11 cases of paralytic poliomyelitis in the United States and four cases in Canada have been accepted as being most probably vaccine-associated.The case of a 35-year-old man who developed paralytic poliomyelitis 17 days after taking oral vaccine is reported. Type III Poliovirus was isolated from his stools, and subsequent virological investigation of this virus strain suggested that it most likely was the attenuated strain. The McBride test gave an NK value of 90 and the rct/40 marker was positive. A rise in Type III antibodies was found in the patient's serum, and increased neurovirulence was demonstrated by intracerebral inoculation of monkeys.Since many cases of neurological involvement have not been accepted as vaccine-associated because of the lack of adequate early investigations, active clinical surveillance after oral polio vaccine administration is urged, and appropriate studies should be carried out in suspect neurological complications.
Changes in Low-Value Services in Year 1 of the Medicare Pioneer Accountable Care Organization Program
Authors: Aaron L. Schwartz, Michael E. Chernew, Bruce E. Landon, J. Michael McWilliams
Journal: JAMA Internal Medicine (2015)

Wasteful practices are widespread in the US health care system. It is unclear if payment models intended to improve health care efficiency, such as the Medicare accountable care organization (ACO) programs, discourage the provision of low-value services.To assess whether the first year of the Medicare Pioneer ACO program was associated with a reduction in use of low-value services.In a difference-in-differences analysis, we compared use of low-value services between Medicare fee-for-service beneficiaries attributed to health care provider groups that entered the Pioneer program (ACO group) and beneficiaries attributed to other health care providers (control group) before (2009-2011) vs after (2012) Pioneer ACO contracts began. Data analysis was conducted from December 1, 2014, to June 27, 2015. Comparisons were adjusted for beneficiaries' sociodemographic and clinical characteristics as well as for geography. We decomposed estimates according to service characteristics (clinical category, price, and sensitivity to patient preferences) and compared estimates between subgroups of ACOs with higher vs lower baseline use of low-value services.Use of, and spending on, 31 services in instances that provide minimal clinical benefit, measured as annual service counts per 100 beneficiaries and price-standardized annual service spending per 100 beneficiaries.During the precontract period, trends in the use of low-value services were similar for the ACO and control groups. The first year of ACO contracts was associated with a differential reduction (95% CI) of 0.8 low-value services per 100 beneficiaries for the ACO group (-1.2 to -0.4; P < .001), corresponding to a 1.9% differential reduction in service quantity (-2.9% to -0.9%) and a 4.5% differential reduction in spending on low-value services (-7.5% to -1.4%; P = .004). Differential reductions were similar for services less sensitive vs more sensitive to patient preferences and for higher- vs lower-priced services. The ACOs with higher than their markets' mean baseline levels of low-value service use experienced greater service reductions (-1.2 services per 100 beneficiaries; -1.7 to -0.7; P < .001) than did ACOs with use below the mean (-0.2 services per 100 beneficiaries, -0.6 to -0.2; P = .41; P = .003 for test of difference between subgroups).During its first year, the Pioneer ACO program was associated with modest reductions in low-value services, with greater reductions for organizations providing more low-value care. Accountable care organization-like risk contracts may be able to discourage use of low-value services even without specifying services to target.
Circulating endothelial cell levels decrease after vasodilator therapy and are a biomarker of clinical worsening in refractory pulmonary hypertension in children
Authors: Marilyne Levy, Damien Bonnet, Laetitia Mauge, Clement d'Audigier, David Celermajer, Pascale Gaussem, David Smadja
Journal: European Respiratory Journal (2012)

BACKGROUND: Pulmonary vasodilators in general and prostacyclin therapy in particular have improved the outcome of patients with pulmonary arterial hypertension (PAH). Endothelial dysfunction is a key feature of PAH and we previously described that circulating endothelial cells (CECs) could be used as a biomarker of endothelial dysfunction in PAH. We now hypothesized that PAH-specific vasodilator therapy might decrease CEC numbers.

METHODS: CECs were quantified by immunomagnetic separation with mAb CD146-coated beads in peripheral blood from children with idiopathic PAH (iPAH, n =30) or PAH secondary to congenital heart disease (PAH-CHD, n =30): before, after treatment and during follow up.

RESULTS: Oral treatment with endothelin antagonists and/or PDE5 inhibitors significantly reduced CEC counts in children. In 10 children with refractory PAH despite oral combination therapy, subcutaneous (SC) treprostinil was added and we observed a significant decrease in CEC counts during the first month of such treatment. CECs were quantified during a 6 to 36 month-follow-up after initiation of SC treprostinil and we found that CEC counts changed over time, with rising counts always preceding clinical deterioration.

CONCLUSIONS: CECs might be useful as a biomarker during follow-up of PAH treatment in pediatric iPAH and PAH-CHD, to assess response to treatment and to anticipate clinical worsening.
Propofol sedation for flexible bronchoscopy in patients with and without chronic obstructive pulmonary disease
Authors: Daiana Stolz, Peter Grendelmeier, Kathleen Jahn, Michael Tamm
Journal: European Respiratory Journal (2013)

Background:  Propofol has been established as a reliable method for conscious sedation in patients undergoing flexible bronchoscopy (FB), but there are scarce data on its safety in patients with COPD. COPD patients can be expected to be at increased risk for sedation related adverse events due to diminished pulmonary reserves.   Methods:  Data from a randomized, controlled trial including 702 patients undergoing FB under propofol sedation administered by trained endoscopy personnel were analysed. Adverse events and complications were prospectively documented.   Results:  COPD was present in 236 cases (33.6%, mean age 63±12.4 y, 65 % male, GOLD IV 20%, III 17%, II 45%). Mean FEV 1 %pred was 57.8%. Mean partial pressure of oxygen was 67.4 mmHg (± 11). COPD patients required similar amounts of propofol in mg/kg KG (p=0.204). As compared to patients without COPD, minor adverse events were significantly more common in COPD (p=0.004), including both SaO 2  ≤90% (p=0.041) and hypotension (BP sys ≤ 90 mmHg, p=0.045). Differences in hypotension but not hypoxemia persisted after adjustment for baseline values. The incidence of complications, including bleeding, intubation, interruption of the procedure, and ICU need were similar in both groups (p=ns for all). There was no death.   Conclusions:  As compared to patients without COPD, minor adverse events during FB and sedation with propofol are more common among COPD patients. Conversely, the incidence of complication is not elevated in patients with COPD.
Intravenous administration of recombinant human macrophage colony-stimulating factor to patients with metastatic cancer: a phase I study.
Authors: M G Sanda, J C Yang, S L Topalian, E S Groves, A Childs, R Belfort, M D de Smet, D J Schwartzentruber, D E White, M T Lotze
Journal: Journal of Clinical Oncology (1992)

PURPOSE Recombinant human macrophage colony-stimulating factor (M-CSF) has been shown to stimulate specifically macrophage lineage differentiation in vitro and to induce cells capable of antitumor activity alone or in combination with an antibody. The administration of M-CSF to mice has demonstrated antitumor therapeutic effects in vivo. Therefore, a phase I trial of M-CSF administration to patients with metastatic cancer was undertaken. PATIENTS AND METHODS M-CSF was given by intermittent intravenous bolus infusion every 8 hours for 7 days; the treatment cycle was repeated once after a week of rest. Cohorts of three patients underwent dose escalation from 10 to 100,000 micrograms/m2/d; 23 patients received 27 courses of M-CSF administration. All patients had metastatic solid tumors refractory to conventional therapy, including renal cell carcinoma (RCC) (nine), melanoma (seven), and colorectal carcinoma (seven). RESULTS Treatment-related toxicity was minimal; five patients developed transient signs of ocular or periorbital inflammation, with iridocyclitis as the most severe manifestation. At the highest doses, platelet counts decreased with therapy (but remained &gt; 100,000/mm3) and the absolute monocyte count increased during the course of therapy. Only at 30,000 and 100,000 micrograms/m2/d was treatment limited because of toxicity (iritis and malaise). Pharmacokinetic studies demonstrated up to a 1,000-fold increase in circulating serum M-CSF after bolus infusion; half-life varied from 1 to 6 hours. Complete regression of mediastinal adenopathy and multiple pulmonary metastases were observed in one patient with RCC. CONCLUSION Recombinant M-CSF can be administered safely to patients with metastatic cancer at doses that demonstrate biologic activity.
Increased systemic inflammation in cystic fibrosis (CF) is associated with deterioration in lung clearance index (LCI)
Authors: Joseph Stuart Elborn, Katherine O'Neill, Elinor Johnston, Judy M. Bradley, Stephen Rowan, Alastair Reid, Michael M. Tunney
Journal: European Respiratory Journal (2014)

LCI is a robust measure of ventilation distribution in CF. There are no data demonstrating a relationship between LCI and biomarkers of systemic inflammation during clinical stability.   Objective : To investigate the relationship between C-reactive protein, (CRP), White Cell Count (WCC) and LCI in CF.  Methods : Stable CF patients from Northern Ireland CF centres, aged ≥ 6 years were recruited. LCI was derived from multiple breath washout. Blood CRP and WCC were measured by turbidimetric immunoassay. Spearman correlation coefficient was used.  Results:  n=83 (table 1).  CRP (figure 1) and WCC (figure 2) had a significant correlation with LCI. Similarly, there was a significant correlation between CRP (r=-0.37; p=0.0006),WCC (r=-0.47; p 1 % pred.   Conclusion:  Increased systemic inflammation in CF is associated with deterioration in LCI.  Funder: US-Ireland Project Partnership Grant.
Leukemogenesis by an Endogenous Virus Isolated From the CFW Mouse. II. Early Effects of Virus on Thymus Gland and Bone Marrow Cell Populations&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Ball Jk
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Leukemogenesis by an Endogenous Virus Isolated From the CFW Mouse. II. Early Effects of Virus on Thymus Gland and Bone Marrow Cell Populations Get access J. K. Ball J. K. Ball 3Cancer Research Laboratory, University of Western Ontario, London, Ontario, Canada N6A 5B7. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 62, Issue 6, June 1979, Pages 1517–1522, https://doi.org/10.1093/jnci/62.6.1517 Published: 01 June 1979 Article history Received: 19 July 1978 Accepted: 18 December 1978 Published: 01 June 1979