tbuckley/cabot-search huggingface dataset:
Single Center Experience of Everolimus Combined with Long-Acting Octreotide in Patients (Pts) with Pretreated Advanced Well Differentiated Neuroendocrine Tumours (Nets) of Different Origin
Authors: V. Gorbunova, A. Kuzminov, N. Orel, A. Markovich, A. Odintsova, A. Mnatsakanyan, G. Emelianova
Journal: Annals of Oncology (2014)
Significant activity of paclitaxel in advanced transitional-cell carcinoma of the urothelium: a phase II trial of the Eastern Cooperative Oncology Group.
Authors: B J Roth, R Dreicer, L H Einhorn, D Neuberg, D H Johnson, J L Smith, G R Hudes, S M Schultz, P J Loehrer
Journal: Journal of Clinical Oncology (1994)

PURPOSE To assess the efficacy and toxicity of single-agent paclitaxel as first-line chemotherapy in patients with locally advanced or metastatic transitional-cell carcinoma of the urothelium. PATIENTS AND METHODS Twenty-six eligible patients were enrolled onto this cooperative group study and treated with paclitaxel at a dosage of 250 mg/m2 by 24-hour continuous infusion every 21 days until progression or patient intolerance. All patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 5 micrograms/kg/d for at least 10 days during each cycle. RESULTS Eleven of 26 patients (42%; 95% confidence interval [CI], 23% to 63%) demonstrated an objective response, with seven achieving a complete clinical response (CR) (27%; 95% CI, 12% to 48%) and four (15%) a partial response (PR). The median duration of response in the 11 responders is 7+ months (range, 4 to 17), with five responders (four CRs, one PR) remaining progression-free at 5, 6, 10, 12, and 16 months from the start of therapy. The estimated median survival duration for all patients is 8.4 months. Hematologic toxicity consisted of anemia (12% grade 3) and granulocytopenia (4% grade 3, 19% grade 4), with two patients developing granulocytopenic fevers. Nonhematologic toxicity included grade 3 mucositis in 11%, grade 3 neuropathy in 11%, and grade 4 diarrhea in 4%. CONCLUSION Single-agent paclitaxel at this dosage and schedule is one of the most active single agents in previously untreated patients with advanced urothelial carcinoma, and is well tolerated by this patient population when given with hematopoetic growth factor support.
C-Type Virus in Bone Marrow Cells of Cats With Myeloproliferative Disorders&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A. Herz, G. H. Theilen, O. W. Schalm, R. J. Munn
Journal: JNCI Journal of the National Cancer Institute (1970)

Clinical and pathological descriptions of 5 cats with myeloproliferative disorders are presented. Electron microscopic studies compared the bone marrow of these 5 cats with 3 clinically normal cats. C-type virus particles, 110–120 mμ in diameter, were found in various types of bone marrow cells of the 5 cats with myeloproliferative disorders. Immature particles budded from the plasmalemma and cytoplasmic vacuolar membranes, whereas mature virions were seen in intercellular spaces and within cytoplasmic vacuoles. These virions were morphologically similar to those known as the causal factor of feline lymphosarcoma. C-type virus was not found in bone marrow cells of 3 clinically normal cats.
Bevacizumab (Bv) in elderly pts with NSCLC: Experience at a tertiary referral center
Authors: Dimitris Vassos, Sofia Tsagouli, Marios Zontanos, Antonis Vassias, Sotiris Tsimpoukis, Paraskevi Boura, Andrianni Charpidou, Konstantinos Syrigos
Journal: European Respiratory Journal (2013)

Background: Bv is a novel anti-angiogenic agent used in many advanced solid tumours, including non-squamous NSCLC. In contrast to clinical studies where enrolled pts are fit, many elderly NSCLC pts suffer from co-morbidities and often have history of a CVD. Methods: Medical records of 2672 pts diagnosed with NSCLC between 2001-2012 were screened. We identified and examined pts ≥75 yrs old treated with bev, for their demographics, clinical data and treatment (Tx) details. We focused on those elderly pts with stable pre-existing cardiovascular disease. Results: 356/2672 NSCLC pts received Bv at any Tx line. 33/382 (8,6%) were ≥75 yrs old. Of those, 29 had various co-morbidities including 19 pts with stable CVD on medical Tx. In the 19 pts with CVD the male:female ratio was 17:2 and mean age 77 yrs (range 75-86). 8/19 pts had impaired renal function. All pts were of Performance Status ECOG 0/1. Median number of Bv cycles was 5 (range 2-11). 17/19 pts experienced ≥1 side effects (11 epistaxis and haemoptysis, 5 proteinuria, 4 hypertension) which led to treatment discontinuation in 5 pts. No major/fatal adverse events were noted. 8/19 pts (42%) showed radiological partial response and 5 (19%) stable disease (total disease control rate 61%). Median survival from initiation of Bv till death/last follow up was 7 months (range 2-28, 95% CI 5.14-12.55). Conclusions: Treatment with Bevacizumab seems to be safe and effective in elderly NSCLC patients with controlled pre-existing cardiovascular disease and good PS. These patients might benefit from participation in clinical trials similarly to younger NSCLC patients.
Abstract 350: High-Mobility Group Protein B2 is Essential in Maintaining Normal Cardiac Gene Expression
Authors: Haodong Chen, Manuel Rosa-Garrido, Ricardo Gray, Zugen Chen, Stanley F Nelson, Sarah Franklin, Emma Monte, Thomas M Vondriska
Journal: Circulation Research (2014)

Heart hypertrophy is a complex disease that involves differential expression of hundreds of genes and requires highly coordinated chromatin remodeling events that must facilitate such genome-wide changes in gene expression. We examine the genome-wide distribution of a chromatin structural protein, High-Mobility Group Protein B2 (HMGB2) in isolated cardiac myocytes with or without adrenergic receptor agonist. We report a comprehensive map of HMGB2 binding in both normal and hypertrophic cardiac myocytes, and find that HMGB2 preferentially localizes to promoters, CpG islands, enhancers and transcription factor binding sites. Moreover, we find that upon hypertrophic stimulation, HMGB2 peaks move from regulatory elements to intergenic regions. Because both HMGB2 knock-down and PHE treatment can induce hypertrophic growth, we compare gene expression dynamics between HMGB2 knock-down and PHE treatment, and find hypertrophy-related gene expression pattern upon HMGB2 knock-down is different from the one after PHE treatment. This also indicates the existence of multiple pathways that lead to hypertrophic growth. Further study reveals that HMGB2 co-localizes with many other functional elements including p300 and CTCF. Interestingly, we find that HMGB2 binding profiles are different at the binding sites of four cardiac transcription factors, MEF2A, NKX2.5, GATA4 and SRF. More specifically, HMGB2 localization is higher at MEF2A binding sites, indicating that HMGB2 may be involved in facilitating the functioning of MEF2A. Finally, we calculate the DNA bendability score based on the primary sequence of genome and correlate it with HMGB2 binding intensity. Consistent with the understanding that HMGB2 bends DNA toward DNA major groove, we find a positive correlation between HMGB2 binding and DNA bending propensity. Surprisingly, PHE treatment in NRVMs induced the relocation of HMGB2 to less bendable intergenic regions. Taken together, our data conclude that HMGB2 is required for maintaining the normal cardiac gene expression pattern, and its binding to cardiac chromatin is dynamically altered during hypertrophic growth.
Glomerulosclerosis in the remnant kidney rat is modulated by dietary alpha-tocopherol.
Authors: S Hahn, N B Kuemmerle, W Chan, S Hisano, P Saborio, R J Krieg, J C Chan
Journal: Journal of the American Society of Nephrology (1998)

Glomerulosclerosis and tubulointerstitial injury are characteristic features seen in the subtotal (5/6) nephrectomy remnant kidney model in the rat. Oxidative stress from renal mass reduction contributes to the glomerular and tubular injury. Previous studies have clearly demonstrated the prevention or inhibition of such injury by an antioxidant such as alpha-tocopherol. However, few data are available on the ability of alpha-tocopherol to modulate or arrest progression of the established disease. This study examines whether alpha-tocopherol modulates glomerulosclerosis and tubulointerstitial injury when it is given 2 wk after renal damage has been established. The findings indicate that alpha-tocopherol has the capacity to modulate both tubulointerstitial injury and glomerulosclerosis, lower the elevated expression of transforming growth factor-beta1, and reduce plasma and kidney malondialdehyde concentration, the end product of lipid peroxidation. The results support the potential utility of alpha-tocopherol in reversing established glomerulosclerosis and tubulointerstitial injury in a remnant kidney model.
Effects of short-term exposure to air pollution on the levels of exhaled nitric oxide among adults - Results from the ADONIX study in Gothenburg, Sweden
Authors: Lars Modig, Santosh Dahgam, Kristina Wass, Fredrik Nyberg, Anna-Carin Olin
Journal: European Respiratory Journal (2012)

The fraction of exhaled nitric oxide (FENO) is a marker of airway inflammation, used clinically to diagnose and monitor asthma. FENO can be measured at different exhalation flows to monitor different parts of the airways. Air pollution is known to cause adverse health effects, and inflammation has been suggested as a main pathway. In this study we examined whether short-term exposure to ozone (O 3 ) ,  nitric oxides (NO x ) or particulate matter less than 10 µm (PM 10 ) are related to increased levels of FENO.  From 2001 through 2008, 5841 randomly selected adults aged 25-75 years in Gothenburg, Sweden, were clinically investigated. FENO was measurement at three different flow-rates, and in this study we included FENO measured at the highest (270ml/s) and lowest (50ml/s) flows. Air pollution data were collected from an urban background station, and we studied the effects of the 3, 24 and 120 hour averages preceding the clinical examination. Log-linear regression was applied to estimate the associations of air pollution on FENO.  One inter-quartile range (IQR) increase in the 120-hr average O 3  levels was associated with a 5.1% (95% CI 1.7-8.5) increase in FENO 270  and 3.6% (95% CI -0.4-3.4) increase in FENO 50 . For NO x  a small effect was seen for the 24- and 120-hr average on FENO 270 , while no clear effect was seen for PM 10 . The effect of ozone on FENO 50  and FENO 270  was significantly lower among asthmatic subjects; however the effect on asthmatics could not be separated from null.  In summary, short-term exposure to O 3  gives rise to a small increase in FENO 270  and FENO 50 , measures of inflammation in the distal and proximal airways.
Variation in care and outcome following myocardial infarction
Authors: Kumar Dharmarajan
Journal: BMJ (2015)

All patients deserve high quality hospital care and the best possible outcome

Research describing variation in hospital treatment and outcomes has improved care for patients with acute myocardial infarction. Studies, particularly from the United States, have shown significant differences in hospitals’ use of evidence based tests and treatments for acute myocardial infarction including aspirin, β blockers, and angiotensin converting enzyme inhibitors.1 In response, major US organizations developed a set of core process measures for treatments considered to be standard of care.2 Hospitals’ performance on these measures were publicly reported and used to guide reimbursement.3 Subsequently, research identified significant variation in hospitals’ outcomes for acute myocardial infarction, including rates of 30 day readmission and mortality.4 The federal government has used hospitals’ performance on these metrics to exact financial penalties on institutions with worse than expected 30 day outcomes.5

It is with this focus on quality of healthcare that Chung and colleagues in the linked paper (doi:10.1136/bmj.h3913) describe variation in guideline recommended treatments and outcomes for patients admitted with acute myocardial infarction in the United Kingdom and Sweden.6 The authors examined nationwide registry data from all hospitals providing care for acute myocardial infarction in both countries between 2004 and 2010. They found that variation in …
The effects of mesechymal cells isolated from abdominal adipose tissue on rat model of emphysema
Authors: Pinar Yildiz Gülhan, Özer Aylin Gürpinar, Mehmet Ekici, Mehmet Niyaz, Muhammet Gülhan, Mustafa Emre Erçin, Aydanur Ekici, Nurkan Aksoy
Journal: European Respiratory Journal (2014)

Emphysema and chronic bronchitis which have different physiopathology, are the significant components of chronic obstructive lung disease (COPD). In emphysema models, it is known that bronchoalveloar lavage fluid (BALF) and matrix metalloproteinaz-9 (MMP-9) in serum are related with emphysema process. There is limited number of study claiming that adipose tissue-derived mesenchymal stem cells (MSC) obtained from have recovering effects on emphysema. The objective of the study is to investigate whether adipose tissue-derived MSCs have recovering effects on emphysema and on MMP-9 levels in an elastase rat model of emphysema.  In this study, 6/8- week-old 31 Wistar albino rats weighing between 250-300 g were assessed. In the first day of study, saline solution was administered intratracheally to the controls (n=10); 0.5 ml saline solution containing 0.1 IU porcine pancreatic elastase (PPE) per body weight in grams was administered intratracheally to the Elastase group (n=12) and the Elastase-MSC group (n=9). Rats in Elastase-MSC group were injected with MSCs suspended in serum physiologic via caudal vein at day 21. In 42nd day of study, all rats were sacrificed. BALF and serum MMP-9 concentrations were measured and emphysema index (EI) was calculated for both lung.  EI median values of Elastase (p=0.008) and Elastase-MSC (p=0.001) groups were significantly lower than that of control group. There was no statistically significant difference between serum and BALF MMP-9 levels of the groups (p>0.005 for two comparisons).  Our findings suggest that treatment with adipose tissue-derived MSC has no effect the serum and BALF MMP-9 levels in emphysematous rats.
Characterization of Two BALB/c Infant Thymus Cell Lines Infected With Lympholeukemogenic Virus<xref ref-type="fn" rid="FN2">2</xref>
Authors: Judith R. Tennant
Journal: JNCI Journal of the National Cancer Institute (1969)

Two morphologically distinct cell culture lines have been established from infant BALB/c thymus tissue initially admixed with the lympholeukemogenic B/T-L virus. The epithelioid cells probably derive from the thymic parenchyma, and the fibroblastic cells from the supporting connective tissue. As evidenced by electron microscopic examinations, both lines produce the virus in large quantity, apparently equally well and without cytopathic effect; but leukemogenicity of virus from these cell cultures is extremely low, suggesting its in vitro attenuation. Line A cells are fast growing, epithelioid, hyperchromic, and polyploid without structural chromosomal abnormalities; they transplant readily to isogeneic mice, producing malignant spindle and giant cell tumors at the site of injection. Line D cells are slow growing, fibroblastic, and hypochromic. Initially diploid (with a metacentric chromosome marker), they become polyploid (to 25%) by passage 25, but do not transplant to isogeneic mice; this line also differs from line A in that the cells are resistant to superinfection with Newcastle disease virus and contain numerous vacuoles, many of them full of Type C particles. The lines are equally susceptible to four other super-infecting viruses, and both are immunogenic in allogeneic mice, resulting in resistance in those mice to isotransplantation of leukemias induced by B/T-L-derived virus. No correlation is made between oncogenicity (transplantability) and the other attributes of these cell lines. Continuous and excessive production of the virus does not prove the thymus to be the in vivo target organ for leukemogenesis by such a virus, but indicates that at least two thymus-derived cell types can effectively support the virus. Earlier studies (J Nat Cancer Inst 36: 599–606, 1966) reported that fresh BALB thymus cells admixed with B/T-L virus inoculum potentiated leukemogenesis in the normally resistant C57BR/cd strain. The mechanism of that potentiation remains a mystery, since cell cultures derived from the same source and demonstrated to carry the same virus did not induce leukemia in C57BR mice in experiments reported here.
Circulating MicroRNA-30d Is Associated With Response to Cardiac Resynchronization Therapy in Heart Failure and Regulates Cardiomyocyte Apoptosis
Authors: Yonathan F. Melman, Ravi Shah, Kirsty Danielson, Junjie Xiao, Bridget Simonson, Andreas Barth, Khalid Chakir, Gregory D. Lewis, Zachary Lavender, Quynh A. Truong, Andre Kleber, Ranendra Das, Anthony Rosenzweig, Yaoyu Wang, David A. Kass, Jagmeet P. Singh, Saumya Das
Journal: Circulation (2015)

Background— Biomarkers that predict response to cardiac resynchronization therapy (CRT) in heart failure patients with dyssynchrony (HF DYS ) would be clinically important. Circulating extracellular microRNAs (miRNAs) have emerged as novel biomarkers that may also play important functional roles, but their relevance as markers for CRT response has not been examined. Methods and Results— Comprehensive miRNA polymerase chain reaction arrays were used to assess baseline levels of 766 plasma miRNAs in patients undergoing clinically indicated CRT in an initial discovery set (n=12) with and without subsequent echocardiographic improvement at 6 months after CRT. Validation of candidate miRNAs in 61 additional patients confirmed that baseline plasma miR-30d was associated with CRT response (defined as an increase in left ventricular ejection fraction ≥10%). MiR-30d was enriched in coronary sinus blood and increased in late-contracting myocardium in a canine model of HF DYS , indicating cardiac origin with maximal expression in areas of high mechanical stress. We examined the functional effects of miR-30d in cultured cardiomyocytes and determined that miR-30d is expressed in cardiomyocytes and released in vesicles in response to mechanical stress. Overexpression of miR-30d in cultured cardiomyocytes led to cardiomyocyte growth and protected against apoptosis by targeting the mitogen-associated kinase 4, a downstream effector of tumor necrosis factor. In HF DYS patients, miR-30d plasma levels inversely correlated with high-sensitivity troponin T, a marker of myocardial necrosis. Conclusions— Baseline plasma miR-30d level is associated with response to CRT in HF DYS in this translational pilot study. MiR-30d increase in cardiomyocytes correlates with areas of increased wall stress in HF DYS and is protective against deleterious tumor necrosis factor signaling.
Inhibition of Ehrlich Ascites Tumor Growth by Nucleoprotein. II. &lt;italic&gt;In Vivo&lt;/italic&gt; Fate of the Tumor Cells
Authors: L Jack Bradshaw, David R. Webb
Journal: JNCI Journal of the National Cancer Institute (1969)

An attempt was made to ascertain whether the inhibition of the Ehrlich ascites tumor in mice by herring-sperm DNA was based on some nonspecific augmentation of the host's immune response. Although some passive transfer experiments indicated a low level of acquired immunity was induced by this procedure, most data ruled out an immunologic explanation. Most significant was the finding that the tumor cells from treated mice could be quantitatively recovered from the animal up to 2 weeks after challenge; these cells were alive and intact. Presumably, the tumor cells were therefore not subjected to phagocytic or immunologic clearing.
Endothelial damage markers in patients with pandemic influenza A (H1N1/09)
Authors: Sergei Lukyanov, Anatoly Govorin, Vladimir Gorbunov, Elena Romanova
Journal: European Respiratory Journal (2012)

Introduction. One of the most important features of influenza A (H1N1) is endothelium damage. In patients with lethal outcomes because of A (H1N1) antigens of a virus in endotheliocytes of pulmonary capillaries were founded (Shieh, W.J. et al. Am. J. Pathol. 2010 177:167-175). Aims and objectives. The aim of the study is to define the value of endothelial damage markers in patients with influenza A (H1N1) in the course of the disease and its outcomes. Methods. 135 patients with pneumonia associated with influenza A (H1N1) during pandemy'2009 were examined in Chita. Of them 58 (group I) were hospitalized to the intensive care units. Group II included 77 patients in the pulmonological department. The virus was verified by the polymerase chain reaction. Plasma level of desquamated endotheliocytes (DEC) and intercellular adhesion molecule-1 (sICAM-1) was determined in all patients, using enzyme-linked immunosorbent assay and immunohistochemistry. For statistical analysis, Mann-Whitney test was applied. Significance was assumed if p value was 0.05. Results. In 44 patients acute respiratory distress-syndrome or acute lung injury (ARDS/ALI) was diagnosed, 20 patients died. The level of DEC and sICAM-1 was elevated in patients of I group - 16 [12,5; 18] and 415 [238; 552] against 8 [6; 10,5] and 219 [179; 338] in group II (p<0.001). The level of DEC and sICAM-1 was considerably raised in patients with ARDS/ALI: 18,5 [16,5; 21] and 525 [372; 672] accordingly. The relative risk of lethal outcome in those patients was 24,4 [3,3; 177]. Conclusion. The high level of DEC and sICAM-1 is associated with severe course of influenza A (H1N1), also with the development of ARDS/ALI and lethal outcomes of the disease.
Radiation in management of patients with dermatofibrosarcoma protuberans.
Authors: H Suit, I Spiro, H J Mankin, J Efird, A E Rosenberg
Journal: Journal of Clinical Oncology (1996)

PURPOSE The preferred treatment of dermatofibrosarcoma protuberans (DFSP) is wide resection, namely, margins &gt; or = 3 cm beyond the evident disease and histologically negative margins. We assess the success achieved by radiation combined with surgery for positive/close margins or by radiation alone for those tumors that are not resectable for technical/medical reasons. The literature on this point is virtually nonexistent. MATERIALS AND METHODS The outcome of treatment of 18 patients with DFSP by radiation alone (n = 3) and radiation and surgery (n = 15) at the Massachusetts General Hospital was assessed. All of the lesions at the time of the treatment by radiation alone or combined with surgery were less than 10 cm. This was the maximum dimension. The actual tumor volume was much less than indicated by this maximum dimension, as the tumors were usually relatively flat. RESULTS The 10-year actuarial local control rate was determined to be 88%. Local control was realized in the three patients treated by radiation alone, with follow-up periods of &gt; or = 9 years. Among 15 patients treated by radiation and surgery, there have been three local failures; the 10-year actuarial local control rate was 84%. The three local failures occurred in 12 patients whose surgical margins were positive. One of these three local failures developed in the group of two patients whose lesions were scored as grade II. CONCLUSION Radiation in well-tolerated dose schedules is an effective option in the management of patients with DFSP. This appears to be true for radiation alone or postoperatively for margin-positive disease (primary or recurrent).