tbuckley/cabot-search huggingface dataset:
Abstract ES2-3: Metabolic asymmetry in breast cancer: Implications for personlised medicine
Authors: MP Lisanti
Journal: Cancer Research (2016)

Abstract Over the last decade, strong evidence has accumulated that the tumor micro-environment plays a key role in recurrence, metastasis and poor clinical outcome in breast cancer patients. In this context, more recent discoveries indicate that catabolic cancer-associated fibroblasts (CAFs) produce nutrients (lactate, ketone bodies and glutamine) to fuel anabolic mitochondrial metabolism in cancer cells. This new paradigm is known as metabolic-symbiosis or metabolic asymmetry and reflects the co-existence of multiple metabolic compartments in a given tumor. This type of metabolic co-operation in the tumor ecosystem underlies the metabolic heterogeneity found in human breast cancers, and can be used to more effectively predict tumor recurrence, metastasis, drug-resistance and poor clinical outcome, in breast cancer patients. In my talk, I will highlight how this metabolic-symbiosis phenotype could be targeted from a therapeutic point of view, bringing us closer to the goal of personalized medicine. For further information on this topic, please see the following references: Caveolae and signalling in cancer. Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Nat Rev Cancer. 2015 Apr;15(4):225-37. Metabolic asymmetry in cancer: A balancing act that promotes tumor growth. Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Cancer Cell. 2014 Jul 14;26(1):5-7. Power surge: Supporting cells fuel cancer cell mitochondria. Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Cell Metab. 2012 Jan 4;15(1):4-5. Citation Format: Lisanti MP. Metabolic asymmetry in breast cancer: Implications for personlised medicine. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr ES2-3.
Nonabsorbable disaccharides for hepatic encephalopathy: A systematic review and meta‐analysis
Authors: Lise L. Gluud, Hendrik Vilstrup, Marsha Y. Morgan
Journal: Hepatology (2016)

Nonabsorbable disaccharides (NADs) have been used to treat hepatic encephalopathy (HE) since 1966. However, a Cochrane Review, published in 2004, found insufficient evidence to recommend their use in this context. This updated systematic review evaluates the effects of the NADs, lactulose and lactitol, for the treatment and prevention of HE in patients with cirrhosis. Thirty-eight randomized controlled trials, involving 1,828 patients, were identified through electronic and manual searches; 31 randomized controlled trials looked at the treatment of HE, while seven looked at its primary/secondary prevention. Random-effects meta-analyses showed that, compared to placebo/no intervention, NADs had a beneficial effect on HE (relative risk [RR] = 0.63, 95% confidence interval [CI] 0.53-0.74, number needed to treat [NNT] = 4) and serious liver-related adverse events such as liver failure, variceal bleeding, serious infections, spontaneous bacterial peritonitis, and hepatorenal syndrome (RR = 0.42, 95% CI 0.26-0.69, NNT = 50). Treatment was also associated with a reduction in mortality in patients with overt HE (RR = 0.36, 95% CI 0.14-0.94, NNT = 20), although not in patients with minimal HE. Meta-analyses of the prevention randomized controlled trials showed that NADs prevented the development of HE (RR = 0.47, 95% CI 0.33-0.68, NNT = 6), the risk of developing serious liver-related adverse events (RR = 0.48, 95% CI 0.33-0.70, NNT = 6), and reduced mortality (RR = 0.63, 95% CI 0.40-0.98, NNT = 20). Use of NADs was associated with nonserious gastrointestinal adverse events. There were no differences in the efficacy or safety of lactulose and lactitol.NADs have beneficial effects in the treatment and prevention of HE; their use, in this context, confers additional benefits including a reduction in serious liver-related morbidities and all-cause mortality. (Hepatology 2016;64:908-922).
Advances in the Prevention and Treatment of<i>Mycobacterium avium</i>Disease
Authors: C. Robert Horsburgh
Journal: New England Journal of Medicine (1996)

Mycobacterium avium complex disease is the third most common opportunistic disease affecting patients with AIDS. In a nationwide survey, it occurred in 22 percent of such patients1; only Pneumocystis carinii pneumonia and Kaposi's sarcoma were more frequent, occurring in 58 percent and 28 percent of patients, respectively. M. avium disease is associated with debilitating symptoms and shortened survival.2 Thus, the reports in this issue of the Journal that document improved regimens for the prevention3,4 and treatment5 of this disease are welcome news.Clarithromycin and azithromycin both have good in vitro activity against M. avium, and it is . . .
Quantitation of Muscle Glycogen Synthesis in Normal Subjects and Subjects with Non-Insulin-Dependent Diabetes by<sup>13</sup>C Nuclear Magnetic Resonance Spectroscopy
Authors: Gerald I. Shulman, Douglas L. Rothman, Thomas Jue, Peter Stein, Ralph A. DeFronzo, Robert G. Shulman
Journal: New England Journal of Medicine (1990)

To examine the extent to which the defect in insulin action in subjects with non-insulin-dependent diabetes mellitus (NIDDM) can be accounted for by impairment of muscle glycogen synthesis, we performed combined hyperglycemic—hyperinsulinemic clamp studies with [13C]glucose in five subjects with NIDDM and in six age- and weight-matched healthy subjects. The rate of incorporation of intravenously infused [1–13C]glucose into muscle glycogen was measured directly in the gastrocnemius muscle by means of a nuclear magnetic resonance (NMR) spectrometer with a 15.5-minute time resolution and a 13C surface coil.
Coffee, Alcohol and Risk of Coronary Heart Disease among Japanese Men Living in Hawaii
Authors: Katsuhiko Yano, George G. Rhoads, Abraham Kagan
Journal: New England Journal of Medicine (1977)

We examined the relation of coffee and alcohol consumption to the risk of coronary heart disease during a six-year period in a cohort of 7705 Japanese men living in Hawaii. The analysis was based on 294 new cases of coronary heart disease. There was a positive association between coffee intake and risk, but it became statistically insignificant when cigarette smoking was taken into account. There was a strong negative association between moderate alcohol consumption (up to 60 ml per day), mainly from beer, and the risk of nonfatal myocardial infarction and death from coronary heart disease. This association remained significant in multivariate analysis, taking into account smoking and other risk factors. The correlation of alcohol consumption with the level of alpha cholesterol (positive) and beta cholesterol (negative) may partly account for the observed negative association between alcohol and coronary heart disease.
Catecholamine metabolism in Gilles de la Tourette's syndrome
Authors: C R Lake, M G Ziegler, R Eldridge, D L Murphy
Journal: American Journal of Psychiatry (1977)

Abnormal central catecholamine neurotransmission has been suggested in Gilles de la Tourette's syndrome. The authors evaluated the sympathetic nervous system in both the basal state and in its responsivity to postural and exercise stress. Plasma norepinephrine and the activities of its synthetic and degradative enzymes were not different in 33 Tourette patients, a control group of unaffected relatives, and another control group of unrelated healthy volunteers. This finding suggests that these patients have neither a generalized dysfunction of norepinephrine metabolism nor a defect in the central control of sympathetic function.
Improved Survival of HER2+ Breast Cancer Patients Treated with Trastuzumab and Chemotherapy Is Associated with Host Antibody Immunity against the HER2 Intracellular Domain
Authors: Keith L. Knutson, Raphael Clynes, Barath Shreeder, Patrick Yeramian, Kathleen P. Kemp, Karla Ballman, Kathleen S. Tenner, Courtney L. Erskine, Nadine Norton, Donald Northfelt, Winston Tan, Carmen Calfa, Mark Pegram, Elizabeth A. Mittendorf, Edith A. Perez
Journal: Cancer Research (2016)

The addition of trastuzumab to chemotherapy extends survival among patients with HER2(+) breast cancer. Prior work showed that trastuzumab and chemotherapy augments HER2 extracellular domain (ECD)-specific antibodies. The current study investigated whether combination therapy induced immune responses beyond HER2-ECD and, importantly, whether those immune responses were associated with survival. Pretreatment and posttreatment sera were obtained from 48 women with metastatic HER2(+) breast cancer on NCCTG (now Alliance for Clinical Trials in Oncology) studies, N0337 and N983252. IgG to HER2 intracellular domain (ICD), HER2-ECD, p53, IGFBP2, CEA, and tetanus toxoid were examined. Sera from 25 age-matched controls and 26 surgically resected HER2(+) patients were also examined. Prior to therapy, some patients with metastatic disease had elevated antibodies to IGFBP2, p53, HER2-ICD, HER2-ECD, and CEA, but not to tetanus toxin, relative to controls and surgically resected patients. Treatment augmented antibody responses to HER2-ICD in 69% of metastatic patients, which was highly associated with improved progression-free survival (PFS; HR = 0.5, P = 0.0042) and overall survival (OS; HR = 0.7, P = 0.038). Augmented antibody responses to HER2-ICD also correlated (P = 0.03) with increased antibody responses to CEA, IGFBP2, and p53, indicating that treatment induces epitope spreading. Paradoxically, patients who already had high preexisting immunity to HER2-ICD did not respond to therapy with increased antibodies to HER2-ICD and demonstrated poorer PFS (HR = 1.6, P < 0.0001) and OS (HR = 1.4, P = 0.0006). Overall, the findings further demonstrate the importance of the adaptive immune system in the efficacy of trastuzumab-containing regimens. Cancer Res; 76(13); 3702-10. ©2016 AACR.
Alternate-Day Prednisone
Authors: David C. Dale, Anthony S. Fauci, Sheldon M. Wolff
Journal: New England Journal of Medicine (1974)

The effects of alternate-day and daily prednisone on leukocyte kinetics were studied in 20 patients with inflammatory diseases to investigate the mechanisms of corticosteroid-induced susceptibility to infections. With daily prednisone, both neutrophil and monocyte inflammatory responses were significantly decreased. In patients on alternate-day prednisone, who were studied during the day on which prednisone was administered, neutrophilia and monocytopenia occurred, and cutaneous inflammatory responses of monocytes, but not of neutrophils, were significantly reduced. On the day of therapy of alternate-day prednisone and with daily therapy the half-life of labeled blood neutrophils was significantly prolonged, and the prolongation was proportional to the dose of the drug given. In contrast, in patients maintained on alternate-day prednisone therapy and studied on the day off drug, leukocyte counts, inflammatory responses and neutrophil half-life were normal. (N Engl J Med 291:1154–1158, 1974)
Search for “Indicators” of Neoplastic Conversion &lt;italic&gt;In Vitro&lt;/italic&gt;
Authors: Katherine K. Sanford, Barbara E. Barker, Mark W. Woods, Ram Parshad, Lloyd W. Law
Journal: JNCI Journal of the National Cancer Institute (1967)

Certain responses of mouse and hamster cells to polyoma virus were examined with respect to their specificity as "indicators" of neoplastic conversion in vitro. These responses included the development of transplantation antigens and changes in morphologic growth pattern, cytology, karyology, rates of proliferation, and glycolytic activities. Under limited conditions, i.e., in short-term, slow-growing cultures, the morphologic change in growth pattern and increases in glycolytic activity and proliferation rate induced by polyoma virus appeared to correlate with neoplastic conversion. However, in long-term or rapidly growing short-term cultures, similar morphologic patterns occurred in cells that subsequently tested as non-neoplastic. Also, such patterns could be induced by polyoma virus in cells already neoplastic. Cells that had undergone "spontaneous" neoplastic conversion frequently showed none of these morphologic features of virus-transformed cells. Prolonged culture of cells without added virus resulted in increased glycolytic activities and proliferation rates equivalent to those of virus-transformed cells. These changes occurred in at least one cell line long before evidence of neoplastic conversion. The cytologic changes in the virus-treated neoplastic cells were similar to those usually associated with neoplastic cells in vivo and may possibly serve as sensitive indicators of in vitro neoplastic conversion. From the observations of this study, the change in morphologic growth pattern is interpreted not as loss of "contact inhibition," but as a proliferative response accompanied by decreased adhesion of cells to the glass substrate.
Effect of Tri-Iodothyronine Replacement on the Metabolic and Pituitary Responses to Starvation
Authors: David F. Gardner, Michael M. Kaplan, Charles A. Stanley, Robert D. Utiger
Journal: New England Journal of Medicine (1979)

To determine the implication of decreased T3 production during fasting, seven normal men were fasted for 80 hours on two occasions; they received 5 microgram of T3 every three hours durnig the second fast. The mean serum T3 concentration declined during the control fast from 120 to 73 ng per deciliter (P less than 0.01), but remained slightly above base-line values during the T3 fast. Mean serum T4 concentrations did not change, and mean serum rT3 concentrations increased, during both fasts. The peak serum TSH increment after TRH was 11.1 micromicron per milliliter before fasting, 8.9 (not significant) after the control fast and 2.2 (P less than 0.01) after the T3 fast. Urea excretion was 9.1 per cent higher during the T3 fast; there were no differences in the changes in blood glucose, plasma fatty acids or other substrates during the two fasts. Pretreatment with potassium iodide lowered serum T4 concentrations and increased the serum TSH response to TRH after fasting. We conclude that the decrease in serum T3 concentrations during fasting spares muscle protein. Fasting is accompanied by a lower set point of TSH secretion, which remains sensitive to changes in serum thyroid hormone concentrations.
Urokinase in Pulmonary Embolism
Authors: Donald E. Tow, Henry N. Wagner, Richard A. Holmes, Katharine S. Harrison, Ursula Scheffel, James K. Langan, Rosemary Longo
Journal: New England Journal of Medicine (1967)

THE use of thrombolytic enzymes or their activators has been proposed as a treatment of thromboembolic diseases such as pulmonary embolism. Using streptokinase as the plasminogen activator, Johnson and McCarty1 demonstrated the efficacy of thrombolytic therapy in the lysis of venous thrombi induced in human volunteers. Fletcher and his associates2 showed in a small clinical trial that this form of therapy was safe and potentially effective. The use of streptokinase has been somewhat limited because of pyrogenicity of the various batches and the intense antigenicity to man.3 Recently, interest has been focussed on urokinase as an activator of thrombolytic enzyme. . . .
Duvelisib (IPI-145), a PI3K-δ,γ Inhibitor, Is Clinically Active in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia
Authors: Susan O'Brien, Manish Patel, Brad S. Kahl, Steven M. Horwitz, Francine M. Foss, Pierluigi Porcu, Jennifer Sweeney, Kerstin Allen, Kerrie Faia, Howard M. Stern, Patrick Kelly, Ian Flinn
Journal: Blood (2014)
Analgesics or pain, who is the real enemy? Suggestions from the CDC guidelines
Authors: Massimo Mammucari
Journal: BMJ (2016)

Responsible use of analgesic drugs is crucial to the management of pain. Proper diagnosis and classification of pain, measurement of its intensity with a validated scale, determination of the type of pain, information on its duration, and identification of comorbidities are essential when selecting analgesics. The …
Abstract 18500: Determinants of Cardiac Loading During Long Duration Spaceflight
Authors: Shigeki Shibata, Jeffrey L Hastings, Shuaib M Abdullah, Michael W Bungo, Steven Platts, Douglas R Hamilton, Benjamin D Levine
Journal: Circulation (2013)

INTRODUCTION: Prolonged exposure to microgravity (bedrest) leads to a decrease in cardiac mass by ~1%/week due to reduced cardiac work. However, the magnitude of reduction with long duration spaceflight with modern countermeasures is unknown. One purpose of this study (Integrated CardioVascular) is to quantify cardiac work and mass in astronauts during 6 months on the International Space Station (ISS). METHODS: Data from 5 astronauts who completed a long duration stay on the ISS (~6 months) were analyzed. Cardiac mass (MRI) was measured pre- and post-flight. Continuous finger blood pressure waveforms (Volume-Clamp) for 24 hours were measured before and the end of flight (15 days before they returned to the earth). Cardiac mass was estimated by (epicardial volume - endocardial volume)*1.05 g/mL. Daily stroke work and cardiac work were calculated by the sum of each stroke volume (ΣSV, SV; stroke voluem) and stroke work (ΣSV*cmBPs, cmBPs; mean central blood pressure during systole) per day, respectively. The central blood pressure waveform was mathematically reconstructed from the finger blood pressure waveform. Beat-to-beat SV was estimated with BP waveform analysis (Modelflow). RESULTS: The %change in cardiac mass was variable (+1% on average) with divergent responses among astronauts (-4%~ +14%). All astronauts showed the reduction of cardiac work (-15±9%), while 4 of 5 showed the reduction of stroke work (-8±12%). A strong positive linear relationship was shown between % changes in cardiac work vs. mass (R 2 =0.471) as well as %changes in stroke work vs. cardiac mass (R 2 =0.905). CONCLUSIONS: Cardiac atrophy during long duration spaceflight is highly dependent on the relative changes in cardiac work and stroke work from preflight to the end of the mission. Current countermeasures may be protective in some, but not all astronauts.
P290 Do lung function indices correlate with risk of pneumothorax following CT-guided biopsy?
Authors: P Griffiths, J Heaton, S Claxton, D Hughes
Journal: Thorax (2015)

<h3>Introduction</h3> CT-guided lung biopsy is a widely used and established technique for the diagnosis of lung lesions, and several risks are well described. The most common complication is pneumothorax, occurring in approximately 20% of cases. We aimed to characterise the risk of post-procedure pneumothorax in our patient population, and determine whether lung function indices correlate with the incidence of pneumothorax. <h3>Methods</h3> Patients undergoing CT-guided biopsy of intraparenchymal lesions from January 2014–2015 were retrospectively identified. Patients were stratified in to those with and without post-procedure pneumothorax. Spirometry and transfer factor for carbon monoxide (TLCO) were reviewed and compared using an unpaired <i>t</i> test. <h3>Results</h3> 111 procedures were performed in 111 patients (53 men 58 women; mean age 70.4 years; range 40 to 88), all done for suspected malignancy. Pneumothorax was identified in 25 patients post biopsy (21%; age range 61 to 87; mean ± SD age, 73.4 ± 6.7), 12 female (48%) and 9 patients (36%) had emphysema. Of the 25 patients with pneumothorax, FEV<sub>1</sub> ranged from 32 to 115% predicted (80.5% ± 23.57%) and FVC ranged from 54 to 125% (91.9% ± 19.1%). TLCO was available for 14 patients, range 34 to 99% predicted (71.5% ± 19.2%). Of the 86 patients with no pneumothorax, FEV1 ranged from 27 to 126% predicted (73.9% ± 29.9%) and FVC ranged from 38 to 139% predicted (85% ± 21.9%). TLCO was available for 50 patients (58%), range 31 to 108% predicted (63.2% ± 18.9%). There was no significant difference in FEV<sub>1</sub> (p = 0.199), FVC (p = 0.109), FEV<sub>1</sub>/FVC ratio (0.99) or TLCO (0.176) between the two groups. In patients developing pneumothorax, those requiring a chest drain (6/25, 24%) showed no significant difference in FEV1 or FVC (p = 0.76 and p = 0.41 respectively) to those managed conservatively. TLCO however was significantly lower in patients requiring chest drain insertion (79% ± 16.1% vs. 52.8% ± 12.8%, p = 0.002). <h3>Conclusion</h3> From our patient group, spirometry data and TLCO showed no correlation with the frequency of pneumothorax. In those patients developing pneumothorax, a low TLCO may predict the need for invasive management.
ATPS-99INTRATUMORAL INJECTION OF AN IN VITRO SYNTHESIZED EFEMP1-DERIVED TUMOR SUPPRESSIVE PROTEIN PRODUCT, ZR30, INTO U251 INTRACRANIAL XENOGRAFTS DEMONSTRATES THERAPEUTIC POTENTIAL IN BRAIN CANCER
Authors: Yi-Hong Zhou, You-Xin Zhou, Xue-Shun Xie, Yanyan Li, Yong Han, Yuan Hu, Mark E. Linskey
Journal: Neuro-Oncology (2015)

BACKGROUND: Therapeutics that could be successful in treating glioblastoma multiforme (GBM) must have multiple tumor suppressive effects targeting the growth and invasion of different tumor cell subpopulations as well as tumor-associated vascularization. Dissection and characterization of functional domains in the EGF-containing fibulin-like extracellular matrix  1 (EFEMP1) identified an EFEMP1 variant named as EFEMP1-derived tumor suppression protein (ETSP), which suppressed the growth of both high-EGFR tumor mass forming cell and low EGFR stem-like tumor initiating cell subpopulations of U251. ZR30 is an in vitro synthesized  product based on the sequence of ETSP with removal of the signal peptide, for use as cancer therapeutic via intratumoral injection. METHODS: Thirty-six mice of similar weight and physical condition, 1 week post-intracranial implantation of U251 (1X105 cells) were randomized into four groups, injected with 5 or 10 µl (350 or 700 ng ZR30) or the same volumes of saline, into the site of the cell implantation, at 10 and 21 days post cell implantation, respectively. RESULTS: Significant improvement in survival of mice treated with ZR30 in comparison with saline given at both time points was observed. CONCLUSIONS: The overall findings from the first in vivo efficacy test support the potential for success in treating brain cancer by applying ZR30 into the resection cavity at the time of completing partial or total tumor removal, and/or continuing to apply it to the surrounding tissue via convection enhanced delivery.