tbuckley/cabot-search huggingface dataset:
Perspectives and potential applications of nanomedicine in breast and prostate cancer
Authors: Yang Liu, Metasebya Solomon, Samuel Achilefu
Journal: Medicinal Research Reviews (2010)

Nanomedicine is a branch of nanotechnology that includes the development of nanostructures and nanoanalytical systems for various medical applications. Among these applications, utilization of nanotechnology in oncology has captivated the attention of many research endeavors in recent years. The rapid development of nano‐oncology raises new possibilities in cancer diagnosis and treatment. It also holds great promise for realization of point‐of‐care, theranostics, and personalized medicine. In this article, we review advances in nano‐oncology, with an emphasis on breast and prostate cancer because these organs are amenable to the translation of nanomedicine from small animals to humans. As new drugs are developed, the incorporation of nanotechnology approaches into medicinal research becomes critical. Diverse aspects of nano‐oncology are discussed, including nanocarriers, targeting strategies, nanodevices, as well as nanomedical diagnostics, therapeutics, and safety. The review concludes by identifying some limitations and future perspectives of nano‐oncology in breast and prostate cancer management. © 2010 Wiley Periodicals, Inc. Med Res Rev
A phase IIIb, multicentre, randomized, double-blind, vehicle-controlled study of the efficacy and safety of adalimumab with and without calcipotriol/betamethasone topical treatment in patients with moderate to severe psoriasis: the BELIEVE study
Authors: D. Thaçi, J.-P. Ortonne, S. Chimenti, P.-D. Ghislain, P. Arenberger, K. Kragballe, J.-H. Saurat, A. Khemis, P. Sprøgel, H.-U. Esslinger, K. Unnebrink, H. Kupper
Journal: British Journal of Dermatology (2010)

Background Data are lacking on the use of topical therapies in combination with tumour necrosis factor blockers for the treatment of psoriasis. Objectives To assess the efficacy and safety of adalimumab (ADA) with topical calcipotriol/betamethasone (C/B) in patients with psoriasis resembling those treated in routine clinical practice. Methods A 16‐week, randomized, vehicle‐controlled trial was conducted in patients with moderate to severe psoriasis and previous failure, intolerance or contraindications to two or more systemic treatments. All patients received ADA (80 mg, week 0; 40 mg every other week, weeks 1–15) in addition to either topical C/B or drug‐free vehicle applied once daily for 4 weeks, and as needed thereafter. The primary endpoint was 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75) at week 16. Results A total of 730 patients received either ADA + C/B (n =366) or ADA + vehicle (n =364). PASI 75 response was initially higher with the combination therapy [14·8% for ADA + C/B vs. 5·8% for ADA + vehicle at week 2 (P <0·001); and 40·7% vs. 32·4%, respectively, at week 4 (P =0·021)]. After week 4, the trend was towards a higher response with ADA monotherapy, with no statistical difference in the PASI 75 response at week 16 (64·8% for ADA + C/B vs. 70·9% for ADA monotherapy, P =0·086). Safety findings were consistent with previous ADA trials. Conclusions ADA + C/B resulted in more rapid and higher efficacy within the first 4 weeks; thereafter, the trend was towards a higher response with ADA monotherapy. There was no statistical difference in the PASI 75 response at week 16. Both treatment regimens were well tolerated.
Utility of serial sputum examinations to discontinue respiratory isolation among inpatients with suspicion of tuberculosis
Authors: Carlos Acuna-Villaorduna, July Lau-deza, Jorge Mora
Journal: European Respiratory Journal (2013)

Background:  Three negative sputum examinations are recommended before discontinuing respiratory isolation for inpatients with suspected pulmonary tuberculosis (PTB); however two sputum examinations could achieve similar efficacy.   Objectives:  To determine the cumulative sensitivity of one, two and three sputum examinations to identify PTB.   Methods:  All inpatients with PTB diagnosed at Washington Hospital Center, DC from January 2000 to August 2009 and Albert Einstein Medical Center at Philadelphia from January 2000 to December 2011 were identified by reviewing the records from the infection control department. Charts were reviewed to determine the number of sputum exams needed to establish the diagnosis. Clinical and radiographic factors were also obtained. The number of extra-cases diagnosed by a third sputum exam and the cumulative sensitivities were estimated   Results:  182 patients with active pulmonary TB were identified as inpatients during the study period. 140 were diagnosed using serial sputum examinations, 35 using bronchoscopy and 7 with lung biopsy.  Out of the 140 patients diagnosed with sputum examinations, 7 were excluded. 133 patients were included. 98 patients were smear positive TB. Out of these, 85 were identified using 1 sputum sample, 11 extra patients were identified with a second sputum sample and 2 extra patient were identified with a third sputum sample. Cumulative sensitivities for serial sputum examinations were: first sputum 85/133 (63.9%), second sputum 96/133 (72.2%), third sputum 98/133 (73.7%)   Conclusion:  The yield of a third sputum exam is very low; only two extra cases were diagnosed in a 10 year period.
Chronic Bioassay of Benzyl Chloride in F344 Rats and (C54BL/6J × BALB/c)F&lt;sub&gt;1&lt;/sub&gt; Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: W Lijinsky
Journal: JNCI Journal of the National Cancer Institute (1986)

Benzyl chloride was administered to groups of 52 male and 52 female F344 rats and (C57BL/6J x BALB/c)F1 mice at two dose levels by gavage in corn oil three times a week for 2 years. Survivors were sacrificed a few weeks later and examined histopathologically. On the basis of a subchronic study at a range of doses, the doses of benzyl chloride in the chronic study were 100 and 50 mg/kg body weight for mice and 30 and 15 mg/kg body weight for rats. In mice of both sexes there was a high and statistically significant incidence of carcinomas and papillomas of the forestomach. In the livers of male mice, but not of females, there was a significantly increased incidence of hepatocellular neoplasms at the low dose but not at the maximally tolerated dose (MTD). In rats the only neoplasms showing a statistically significant increase compared with controls were C-cell neoplasms of the thyroid gland in females. A significant incidence of neoplasms was not found in the forestomachs of F344 rats, but it is possible that true MTD was not used for rats.
Effect of Dietary Fat on X-Ray-Induced Mammary Cancer in Sprague-Dawley Rats&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: Jerald Silverman, Claire J. Shellabarger, Seymour Holtzman, J. Patrick Stone, John H. Weisburger
Journal: JNCI Journal of the National Cancer Institute (1980)

We studied the effect of dietary fat levels on the induction of mammary cancer by 350 rads total-body X-radiation given to noninbred albino Sprague-Dawley rats at 50 days of age. Compared to rats on a Sow-fat (LF) diet (5% lard), rats on a high-fat (HF) diet (20% lard) from 30 days of age had more tumors, with a higher multiplicity of carcinomas per rat. LF-fed groups exhibited a longer median tumor latency period than did HF-fed groups. A similar trend toward more tumors with an earlier time of death was seen in rats given single iv doses of 50 mg 1-methyl-1-nitrosourea/kg and fed an HF diet as compared to an LF diet.
Abstract P034: Circulating Omega-3 Fatty Acids and Risk of Acute Myocardial Infarction in Singapore Chinese
Authors: Ye Sun, Woon-Puay Koh, Jian-Min Yuan, Hyungwon Choi, Choon Nam Ong, Rob M van Dam
Journal: Circulation (2015)

Introduction: Omega-3 fatty acids have been associated with reduced risk of coronary heart disease, but it remains unclear whether plant-based alpha-linolenic acid (ALA) provide similar benefits as marine-originated eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and evidence from Asian populations is limited. Objective: We aimed to examine the association between plasma omega-3 fatty acid biomarkers, including ALA, EPA and DHA, and risk of acute myocardial infarction (AMI) in a Chinese population in Singapore, and to explore the potential biological mediators of their effects. Methods: We conducted a nested case control study with 759 incident fatal and non-fatal AMI cases and 796 matched controls selected from the Singapore Chinese Health Study, who were of ages 45-74 at the time of recruitment and free of cardiovascular disease at the time of blood collection. Plasma fatty acid biomarkers were measured using gas chromatography tandem mass spectrometry. Conditional logistic regression was us...
Prognostic implications of delayed heart rate recovery from maximal-incremental exercise in patients with pulmonary arterial hypertension
Authors: Roberta Pulcheri Ramos, Jaquelina Sonoe Ota Arakaki, Priscila Barbosa, Erika Treptow, Fabricio Martins Valois, Eloara Vieira Machado Ferreira, Luiz Eduardo Nery, J. Alberto Neder
Journal: European Respiratory Journal (2012)

Rationale:  Early recovery from exercise is characterized by a marked reduction in heart rate (HR) due to sudden reintroduction of vagal tone and progressive withdrawal of sympathetic stimulation. HR recovery (HRR) is delayed in pulmonary arterial hypertension (PAH), a disabling condition associated with autonomic imbalance.  Objective : To investigate the usefulness of HRR to estimate exercise impairment and prognosis in PAH patients.  Methods : We evaluated 72 patients with PAH of varied aetiology (NYHA class I to IV) and 21 age- and gender-matched controls who underwent a maximal incremental cardiopulmonary exercise test (CPET) with HR being recorded up to the 5th minute of recovery.  Results:  HRR was consistently lower in patients compared to controls (p 1min ) to discriminate patients from controls was 18 beats (AUC 0.76 [0.66-0.86], p  1min  was associated with a range of maximal and sub-maximal variables indicative of better preserved exercise tolerance (p 1min  was the single predictor of mortality (hazard ratio (95% confidence interval)= 1.19 (1.03-1.37); p Conclusions : Preserved HRR 1min  (>18 beats) is associated with less impaired responses to exercise in patients with PAH. Conversely, an abnormal HRR 1min  response has negative prognostic implications, a finding likely to be clinically useful when more sophisticated analyses provided by a full CPET are not readily available.
Histopathology of Tumor Regression After Intralesional Injection of Mycobacferium bovis . IV. Development of Immunity to Tumor Cells and BCG 2
Authors: M. G. Hanna, M. J. Snodgrass, B. Zbar, H. J. Rapp
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Histopathology of Tumor Regression After Intralesional Injection of Mycobacferium bovis. IV. Development of Immunity to Tumor Cells and BCG Get access M. G. Hanna, Jr., M. G. Hanna, Jr. 3Carcinogenesis Program, Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tenn. 37830 Search for other works by this author on: Oxford Academic PubMed Google Scholar M. J. Snodgrass, M. J. Snodgrass 3Carcinogenesis Program, Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tenn. 37830 Search for other works by this author on: Oxford Academic PubMed Google Scholar B. Zbar, B. Zbar 4Biology Branch, Carcinogenesis Program, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar H. J. Rapp H. J. Rapp 4Biology Branch, Carcinogenesis Program, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 6, December 1973, Pages 1897–1908, https://doi.org/10.1093/jnci/51.6.1897 Published: 01 December 1973 Article history Received: 25 May 1973 Accepted: 08 August 1973 Published: 01 December 1973
Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points.
Authors: I F Tannock, D Osoba, M R Stockler, D S Ernst, A J Neville, M J Moore, G R Armitage, J J Wilson, P M Venner, C M Coppin, K C Murphy
Journal: Journal of Clinical Oncology (1996)

To investigate the benefit of chemotherapy in patients with symptomatic hormone-resistant prostate cancer using relevant end points of palliation in a randomized controlled trial.We randomized 161 hormone-refractory patients with pain to receive mitoxantrone plus prednisone or prednisone alone (10 mg daily). Nonresponding patients on prednisone could receive mitoxantrone subsequently. The primary end point was a palliative response defined as a 2-point decrease in pain as assessed by a 6-point pain scale completed by patients (or complete loss of pain if initially 1 +) without an increase in analgesic medication and maintained for two consecutive evaluations at least 3 weeks apart. Secondary end points were a decrease of > or = 50% in use of analgesic medication without an increase in pain, duration of response, and survival. Health-related quality of life was evaluated with a series of linear analog self-assessment scales (LASA and the Prostate Cancer-Specific Quality-of-Life Instrument [PROSQOLI]), the core questionnaire of the European Organization for Research and Treatment of Cancer (EORTC), and a disease-specific module.Palliative response was observed in 23 of 80 patients (29%; 95% confidence interval, 19% to 40%) who received mitoxantrone plus prednisone, and in 10 of 81 patients (12%; 95% confidence interval, 6% to 22%) who received prednisone alone (P = .01). An additional seven patients in each group reduced analgesic medication > or = 50% without an increase in pain. The duration of palliation was longer in patients who received chemotherapy (median, 43 and 18 weeks; P < .0001, log-rank). Eleven of 50 patients randomized to prednisone treatment responded after addition of mitoxantrone. There was no difference in overall survival. Treatment was well tolerated, except for five episodes of possible cardiac toxicity in 130 patients who received mitoxantrone. Most responding patients had an improvement in quality-of-life scales and a decrease in serum prostate-specific antigen (PSA) level.Chemotherapy with mitoxantrone and prednisone provides palliation for some patients with symptomatic hormone-resistant prostate cancer.
Lymphoscintigraphy of Human Colorectal Carcinoma Metastases in Athymic Mice by Use of Radioiodinated B72.3 Monoclonal Antibody&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Sudhir A. Shah, Brian M. Gallagher, Howard Sands
Journal: JNCI Journal of the National Cancer Institute (1987)

The potential of radioiodinated monoclonal antibody B72.3 for lymphoscintigraphy was evaluated, using suitable animal models of a human colorectal carcinoma. LS174T xenografts were grown at various sites in β-estradiol-pretreated athymic mice, and the development of metastases in different organs was assessed histologically. After iv inoculation of the mice, 66% of the animals developed “metastases” to the axillary lymph nodes. Of these mice, 100% also developed multiple tumors on their backs and 79% had lung micrometastases. Livers, kidneys, and spleens showed no evidence of tumor growth. In 33% of the mice in which primary LS174T tumors had been removed from the hindfoot pad, metastases to the popliteal lymph nodes were observed 3½ weeks after tumor implantation. BALB/c (nu/nu) female mice bearing axillary and popliteal lymph node metastases were used to test the potential of radiolabeled B72.3 antibody (an IgG1) as a lymphoscinti-graphic agent. A monoclonal antibody against horseradish peroxidase (also an IgG1), which did not bind LS174T tumor cells in vitro, served as a control. Both normal and tumor-bearing axillary and popliteal lymph nodes imaged up to 6 hours after the sc injection of 20–40 μ of 125I-labeled B72.3 into either the forefoot or hindfoot pads. The localization index (L.I.) (specific/nonspecific antibody in tumor divided by specific/nonspecific antibody in blood) for LS174T tumors in lymph nodes was approximately 1 during the first 6 hours after antibody injection, thus indicating no specific antibody accumulation. Twenty-four hours and later after sc injection, images of nodal metastases (14–477 mg) and specific antibody accumulations were observed. At these times the L.I.'s ranged 1.5–3.5. Tumor-negative nodes did not image at 24 hours after injection of 125l-labeled B72.3. The L.I.'s of the normal nodes and of other tissues from these mice were about 1.0 at 24 hours, indicating no specific antibody accumulation. Autoradiographic analysis of lymph nodes containing LS174T tumor showed heterogeneous antibody distribution of B72.3 within tumor sections with heavy patches of antibody accumulation in mucin globules. In lymph nodes the normal lymphocytes adjacent to the LS174T tumor cells showed no antibody accumulation. The lack of specific, early antibody accumulation by LS174T tumor-bearing nodes in mice suggests that B72.3 does not accumulate in nodal metastases to the degree necessary to consider it a potential agent for use in lymphoscintigraphy.
Induction of Antitumor Cytotoxicity of Normal Syngeneic and Allogeneic Lymphocytes by Methotrexate
Authors: Zaira G. Kadaghidze, George J. Svet-Moldavsky
Journal: JNCI Journal of the National Cancer Institute (1971)

Journal Article Induction of Antitumor Cytotoxicity of Normal Syngeneic and Allogeneic Lymphocytes by Methotrexate Get access Zaira G. Kadaghidze, Zaira G. Kadaghidze Laboratory of Virology, Institute of Experimental and Clinical Oncology, Academy of Medical Sciences, Moscow, USSR Search for other works by this author on: Oxford Academic PubMed Google Scholar George J. Svet-Moldavsky, M.D. George J. Svet-Moldavsky, M.D. Laboratory of Virology, Institute of Experimental and Clinical Oncology, Academy of Medical Sciences, Moscow, USSR Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 46, Issue 5, May 1971, Pages 921–928, https://doi.org/10.1093/jnci/46.5.921 Published: 01 May 1971 Article history Received: 07 April 1970 Accepted: 06 January 1971 Published: 01 May 1971
Exercise capacity and lobar hyperinflation in patients with COPD
Authors: Glenn Leemans, Kris Ides, Cedric Van Holsbeke, Wim Vos, Jan De Backer, Wilfried De Backer
Journal: European Respiratory Journal (2013)

Introduction 

Reduced exercise capacity in COPD patients can be due to lung hyperinflation. Until recently, this could only be measured by pulmonary function tests (PFT) which are not capable to measure regional lung changes. However, CT based Functional Respiratory Imaging (FRI) is able to quantify hyperinflation on a lobar level. These regional lung changes and their relationship with exercise capacity remained so far unexplored.

Objective 

To evaluate the relationship between lobar hyperinflation and exercise capacity.

Methods 

A retrospective analysis of baseline data on 26 COPD patients was performed. Patients underwent PFT. Exercise capacity was measured by 6 minute walking test. Lobar hyperinflation was measured by FRI. Based on CT, three dimensional models of the lobes were extracted and hyperinflation was calculated at functional residual capacity.

Results 

Lung hyperinflation by PFT, expressed as the ratio between residual volume and total lung capacity (RV/TLC), is inversely correlated with 6 minute walking distance (6MWD)(Spearman r=-0.591; p=0.001), whereas lobar hyperinflation of only the left upper lobe is correlated with the 6MWD (Spearman r=0.422; p=0.032).

![Figure][1] 



Conclusions 

FRI is more sensitive to measure the regional changes in the lung than PFT (De Backer, L. et al. ERJ 2012; 40:298-305), however lobar hyperinflation does not contribute to exercise capacity. It seems that exercise capacity is more related to global changes in lung impairment.

 [1]: pending:yes
Formoterol, a new long-acting bronchodilator for inhalation
Authors: P Arvidsson, S Larsson, CG Lofdahl, B Melander, L Wahlander, N Svedmyr
Journal: European Respiratory Journal (1989)

The aim of this study was to evaluate if treatment with inhaled formoterol is appreciated by asthmatics and whether it causes tachyphylaxis. Twenty stable asthmatics were included in a randomized, double-blind, crossover study. They were treated for two weeks either with formoterol or salbutamol, with one week washout inbetween. They were given 12 micrograms formoterol or 200 micrograms salbutamol twice daily and instructed to use additional spray doses on demand. On a diary card they recorded the number of doses, asthma symptoms and peak expiratory flow rate (PEFR) before every dose. Forced expiratory volume in one second (FEV1) dose-response curves for salbutamol (total dose 1.3 mg) were performed before and after each treatment period to evaluate development of tachyphylaxis. There was a significant difference in favour of formoterol concerning symptoms, PEFR recordings, spray consumption, and preference. Fifteen patients preferred formoterol and two salbutamol. The dose-response curves before formoterol and before, as well as after salbutamol were almost identical. After formoterol the curve had changed; both basal and maximum values were higher than before. Thus, no evidence of tachyphylaxis was found, compared to the ordinary beta-stimulant treatment.
Decreased affinity for efflux transporters increases brain penetrance and molecular targeting of a PI3K/mTOR inhibitor in a mouse model of glioblastoma
Authors: C. M. Becker, R. K. Oberoi, S. J. McFarren, D. M. Muldoon, D. H. Pafundi, J. L. Pokorny, D. H. Brinkmann, J. R. Ohlfest, J. N. Sarkaria, D. A. Largaespada, W. F. Elmquist
Journal: Neuro-Oncology (2015)

Targeting drug delivery to invasive glioma cells is a particularly difficult challenge because these cells lie behind an intact blood-brain barrier (BBB) that can be observed using multimodality imaging. BBB-associated efflux transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) influence drug distribution to these cells and may negatively impact efficacy. To test the hypothesis that efflux transporters influence brain pharmacokinetics/pharmacodynamics of molecularly targeted agents in glioma treatment, we assessed region-specific penetrance and molecular-targeting capacity for a PI3K/mTOR kinase inhibitor that has high substrate affinity for efflux transporters (GDC-0980) and an analog (GNE-317) that was purposely designed to have reduced efflux. Brain tumor penetrance of GDC-0980 and GNE-317 was compared between FVB/n wild-type mice and Mdr1a/b−/−Bcrp−/− triple-knockout mice lacking P-gp and BCRP. C57B6/J mice bearing intracranial GL261 tumors were treated with GDC-0980, GNE-317, or vehicle to assess the targeted pharmacokinetic/pharmacodynamic effects in a glioblastoma model. Animals treated with GNE-317 demonstrated 3-fold greater penetrance in tumor core, rim, and normal brain compared with animals dosed with GDC-0980. Increased brain penetrance correlated with decreased staining of activated p-Akt, p-S6, and p-4EBP1 effector proteins downstream of PI3K and mTOR. GDC-0980 is subject to active efflux by P-gp and BCRP at the BBB, while brain penetrance of GNE-317 is independent of efflux, which translates into enhanced inhibition of PI3K/mTOR signaling. These data show that BBB efflux by P-gp and BCRP is therefore an important determinant in both brain penetrance and molecular targeting efficacy in the treatment of invasive glioma cells.