tbuckley/cabot-search huggingface dataset:
Docetaxel Followed by Hormone Therapy in Men Experiencing Increasing Prostate-Specific Antigen After Primary Local Treatments for Prostate Cancer
Authors: Arif Hussain, Nancy Dawson, Pradip Amin, Christine Engstrom, Brenda Dorsey, Eliot Siegel, Chuanfa Guo
Journal: Journal of Clinical Oncology (2005)

Prostatectomy or radiation for localized prostate cancer (PC) can fail in up to 15% to 30% of patients. The purpose of this study was to determine feasibility, tolerability, and outcome of docetaxel followed by hormone therapy in men experiencing an increasing prostate-specific antigen (PSA) after their primary local treatments for PC.Men with increasing serum PSA after prostatectomy or/and radiation were eligible. Serum PSA had to be > or = 4 ng/mL and serum testosterone had to be in the noncastrate range. Treatment included docetaxel 70 mg/m2 every 3 weeks for up to six cycles, followed by total androgen suppression (luteinizing hormone-releasing hormone agonist plus bicalutamide) and peripheral androgen blockade (finasteride plus bicalutamide) for 12 to 20 months.Thirty-nine men were enrolled; 32 had PSA-only failure, seven also had clinical metastasis. Baseline median PSA was 13.7 ng/mL. Serum PSA decreased > or = 50% in 17 of 35 patients (48.5%) and > or = 75% in seven of 35 patients (20%) with docetaxel. The PSA decreased to a median of 0.1 ng/mL with subsequent hormone therapy. In 28 of 33 patients the PSA increased (median, 0.41 ng/mL) at a median follow-up of 2.3 months after treatment. In contrast, in five of 33 men the PSA remains at 0.1 ng/mL at a median of 18.9 months after therapy; three of these five men had soft tissue metastasis at entry but remain in complete remission. The most common grade 3 to 4 toxicity was neutropenia (61.5%).Docetaxel followed by hormone therapy of limited duration may provide disease control in subgroups of men experiencing failure after local treatments for PC.
Retreatment with Bendamustine in Patients with Relapsed/Refractory Indolent B-Cell Lymphoma and Mantle Cell Lymphoma
Authors: Toshiki Yamada, Nobuhiko Nakamura, Jun-ichi Kitagawa, Nobuhiro Kanemura, Naoe Goto, Senji Kasahara, Hideko Goto, Kenji Fukuno, Takeshi Hara, Hisashi Tsurumi
Journal: Annals of Oncology (2014)
Sympathetic Innervation of the Developing Rabbit Heart
Authors: WILLIAM F. FRIEDMAN, PETER E. POOL, DAVID JACOBOWITZ, SHIRLEY C. SEAGREN, EUGENE BRAUNWALD
Journal: Circulation Research (1968)

The sympathetic innervation of the rabbit heart, as a function of age, was studied by measuring the cardiac concentration of catecholamines and observing the anatomic distribution of sympathetic nerves by the monoamine fluorescense technique. The cardiac concentration of norepinephrine in late gestation was quite low; the levels rose progressively after birth to reach adult levels by about three weeks of age. Similar small amounts of epinephrine were found in the hearts at all ages. Substantially less change in adrenal catecholamines accompanied advancing age. At all ages a close correlation was noted between the norepinephrine levels and the histochemical demonstration of sympathetic innervation. Intensely fluorescent, terminal varicosities were observed within large preterminal nerve trunks only in the youngest animals, suggesting that the sympathetic nerves move into, rather than form within, the heart. Chromaffin cells were observed in the hearts at all ages.
The mesangial phagocyte and its regulation of contractile cell biology.
Authors: G F Schreiner
Journal: Journal of the American Society of Nephrology (1992)

The mesangium constitutes the core of the renal glomerulus. It consists of the matrix, composed of mucopolysaccharides and glycoproteins, and two cell types. The predominant cell type is the mesangial cell, resembling a vascular smooth muscle cell. Up to 15% of the mesangial cell population additionally consists of resident mesangial phagocytes. These are derived from the bone marrow and belong to the family of mononuclear leukocytes. They are phagocytic, express Fc and C3 receptors, and display membrane Ia antigens. They syngeneically stimulate lymphocyte proliferation via antigen presentation. They are equally potent allogeneic stimulating cells in mixed lymphocyte culture. The mesangium is also the preferred locus of the induced migration of monocytes in inflammatory and proteinuric states. The presence of both normally resident and inflammation-associated mesangial phagocyte is lipid dependent. Hyperlipidemia increases the population of mesangial phagocytes. Lipid restriction decreases their number and, as a result, diminishes the allogenicity of renal transplants and blunts the progression of glomerulonephritis. One signal regulating the infiltration of the mesangium by mononuclear phagocytes appears to be a complex neutral lipid that is highly and specifically chemotactic for monocytes. It is released by the contractile mesangial cell in response to the stimulation of its Fc receptor and to the mesangial deposition of macromolecules. Both resident and inflammatory mesangial phagocytes secrete factors that remodel the mesangial matrix, stimulate mesangial cell proliferation, alter glomerular basement membrane permeability, and regulate blood flow. The persistence of mononuclear phagocytes in an activated state within the mesangium contributes to the marked alteration in mesangial structure that eventuates in glomerulosclerosis in both immune and nonimmune models of glomerular injury.
Viral Escape by Selection of Cytotoxic T Cell–Resistant Variants in Influenza a Virus Pneumonia
Authors: Graeme E. Price, Rong Ou, Hong Jiang, Lei Huang, Demetrius Moskophidis
Journal: The Journal of Experimental Medicine (2000)

Antigenic variation is a strategy exploited by influenza viruses to promote survival in the face of the host adaptive immune response and constitutes a major obstacle to efficient vaccine development. Thus, variation in the surface glycoproteins hemagglutinin and neuraminidase is reflected by changes in susceptibility to antibody neutralization. This has led to the current view that antibody-mediated selection of influenza A viruses constitutes the basis for annual influenza epidemics and periodic pandemics. However, infection with this virus elicits a vigorous protective CD8+ cytotoxic T lymphocyte (CTL) response, suggesting that CD8+ CTLs might exert selection pressure on the virus. Studies with influenza A virus–infected transgenic mice bearing a T cell receptor (TCR) specific for viral nucleoprotein reveal that virus reemergence and persistence occurs weeks after the acute infection has apparently been controlled. The persisting virus is no longer recognized by CTLs, indicating that amino acid changes in the major viral nucleoprotein CTL epitope can be rapidly accumulated in vivo. These mutations lead to a total or partial loss of recognition by polyclonal CTLs by affecting presentation of viral peptide by class I major histocompatibility complex (MHC) molecules, or by interfering with TCR recognition of the mutant peptide–MHC complex. These data illustrate the distinct features of pulmonary immunity in selection of CTL escape variants. The likelihood of emergence and the biological impact of CTL escape variants on the clinical outcome of influenza pneumonia in an immunocompetent host, which is relevant for the design of preventive vaccines against this and other respiratory viral infections, are discussed.
Resveratrol Does Not Benefit Patients With Nonalcoholic Fatty Liver Disease
Authors: Veronique S. Chachay, Graeme A. Macdonald, Jennifer H. Martin, Jonathan P. Whitehead, Trisha M. O'Moore–Sullivan, Paul Lee, Michael Franklin, Kerenaftali Klein, Paul J. Taylor, Maree Ferguson, Jeff S. Coombes, Gethin P. Thomas, Gary J. Cowin, Carl M.J. Kirkpatrick, Johannes B. Prins, Ingrid J. Hickman
Journal: Clinical Gastroenterology and Hepatology (2014)
PIAS1 interacts with FLASH and enhances its co-activation of c-Myb
Authors: Anne Hege Alm-Kristiansen, Petra I Lorenzo, Ann-Kristin Molværsmyr, Vilborg Matre, Marit Ledsaak, Thomas Sæther, Odd S Gabrielsen
Journal: Molecular Cancer (2011)

FLASH is a huge nuclear protein involved in various cellular functions such as apoptosis signalling, NF-κB activation, S-phase regulation, processing of histone pre-mRNAs, and co-regulation of transcription. Recently, we identified FLASH as a co-activator of the transcription factor c-Myb and found FLASH to be tightly associated with active transcription foci. As a huge multifunctional protein, FLASH is expected to have many interaction partners, some which may shed light on its function as a transcriptional regulator.To find additional FLASH-associated proteins, we performed a yeast two-hybrid (Y2H) screening with FLASH as bait and identified the SUMO E3 ligase PIAS1 as an interaction partner. The association appears to involve two distinct interaction surfaces in FLASH. We verified the interaction by Y2H-mating, GST pulldowns, co-IP and ChIP. FLASH and PIAS1 were found to co-localize in nuclear speckles. Functional assays revealed that PIAS1 enhances the intrinsic transcriptional activity of FLASH in a RING finger-dependent manner. Furthermore, PIAS1 also augments the specific activity of c-Myb, and cooperates with FLASH to further co-activate c-Myb. The three proteins, FLASH, PIAS1, and c-Myb, are all co-localized with active RNA polymerase II foci, resembling transcription factories.We conclude that PIAS1 is a common partner for two cancer-related nuclear factors, c-Myb and FLASH. Our results point to a functional cooperation between FLASH and PIAS1 in the enhancement of c-Myb activity in active nuclear foci.
Molecular Characterization of Neuroendocrine Prostate Cancer and Identification of New Drug Targets
Authors: Himisha Beltran, David S. Rickman, Kyung Park, Sung Suk Chae, Andrea Sboner, Theresa Y. MacDonald, Yuwei Wang, Karen L. Sheikh, Stéphane Terry, Scott T. Tagawa, Rajiv Dhir, Joel B. Nelson, Alexandre de la Taille, Yves Allory, Mark B. Gerstein, Sven Perner, Kenneth J. Pienta, Arul M. Chinnaiyan, Yuzhuo Wang, Colin C. Collins, Martin E. Gleave, Francesca Demichelis, David M. Nanus, Mark A. Rubin
Journal: Cancer Discovery (2011)

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer that most commonly evolves from preexisting prostate adenocarcinoma (PCA). Using Next Generation RNA-sequencing and oligonucleotide arrays, we profiled 7 NEPC, 30 PCA, and 5 benign prostate tissue (BEN), and validated findings on tumors from a large cohort of patients (37 NEPC, 169 PCA, 22 BEN) using IHC and FISH. We discovered significant overexpression and gene amplification of AURKA and MYCN in 40% of NEPC and 5% of PCA, respectively, and evidence that that they cooperate to induce a neuroendocrine phenotype in prostate cells. There was dramatic and enhanced sensitivity of NEPC (and MYCN overexpressing PCA) to Aurora kinase inhibitor therapy both in vitro and in vivo, with complete suppression of neuroendocrine marker expression following treatment. We propose that alterations in Aurora kinase A and N-myc are involved in the development of NEPC, and future clinical trials will help determine from the efficacy of Aurora kinase inhibitor therapy.We report on the largest in-depth molecular analysis of NEPC and provide new insight into molecular events involved in the progression of prostate cancer.
Is there a relationship between subacromial impingement syndrome and scapular orientation? A systematic review
Authors: Elizabeth Ratcliffe, Sharon Pickering, Sionnadh McLean, Jeremy Lewis
Journal: British Journal of Sports Medicine (2013)

Background Alterations in scapular orientation and dynamic control, specifically involving increased anterior tilt and downward rotation, are considered to play a substantial role in contributing to a subacromial impingement syndrome (SIS). Non-surgical intervention aims at restoring normal scapular posture. The research evidence supporting this practice is equivocal. Objective The aim of this study was to systematically review the relevant literature to examine whether a difference exists in scapular orientation between people without shoulder symptoms and those with SIS. Data sources MEDLINE, AMED, EMBASE, CINAHL, PEDro and SPORTDiscus databases were searched using relevant search terms up to August 2013. Additional studies were identified by hand-searching the reference lists of pertinent articles. Review methods Of the 7445 abstracts identified, 18 were selected for further analysis. Two reviewers independently assessed the studies for inclusion, data extraction and quality, using a modified Downs and Black quality assessment tool. Results 10 trials were included in the review. Scapular position was determined through two-dimensional radiological measurements, 360° inclinometers and three-dimensional motion and tracking devices. The findings were inconsistent. Some studies reported patterns of reduced upward rotation, increased anterior tilting and medial rotation of the scapula. In contrast, others reported the opposite, and some identified no difference in motion when compared to asymptomatic controls. Conclusions The underlying aetiology of SIS is still debated. The results of this review demonstrated a lack of consistency of study methodologies and results. Currently, there is insufficient evidence to support a clinical belief that the scapula adopts a common and consistent posture in SIS. This may reflect the complex, multifactorial nature of the syndrome. Additionally, it may be due to the methodological variations and shortfalls in the available research. It also raises the possibility that deviation from a ‘normal’ scapular position may not be contributory to SIS but part of normal variations. Further research is required to establish whether a common pattern exists in scapular kinematics in SIS patients or whether subgroups of patients with common patterns can be identified to guide management options. Non-surgical treatment involving rehabilitation of the scapula to an idealised normal posture is currently not supported by the available literature.
Pharmacogenomics in Early-Phase Oncology Clinical Trials: Is There a Sweet Spot in Phase II?
Authors: Peter H. O'Donnell, Walter M. Stadler
Journal: Clinical Cancer Research (2012)

Many clinical trials of oncology drugs now include at least a consideration of pharmacogenomics, the study of germline or acquired genetic factors governing a drug's response and toxicity. Besides the potential benefit to patients from the consideration of personalized pharmacogenomic information when making treatment decisions, the incentive is clear for oncology drug developers to incorporate pharmacogenomic factors in the drug development process, because pharmacogenomic biomarkers may allow predictive characterization of subpopulations within a disease that may particularly respond or may allow preidentification of patients at highest risk for adverse events. There is, however, a lack of agreement in actual practice about at what point in the oncology clinical drug development process pharmacogenomic studies should be incorporated. In this article, we examine the recent growth of pharmacogenomics in oncology clinical trials, especially in early-phase studies, and examine several critical questions facing the incorporation of pharmacogenomics in early oncologic drug development. We show that phase II clinical trials, in particular, have a favorable track record for showing positive pharmacogenomic signals, worthy of additional follow-up and validation, and that the phase II setting holds significant promise for potentially accelerating and informing future phase III trials. We conclude that phase II trials offer an ideal "sweet spot" for routine incorporation of pharmacogenomic questions in oncology drug development.
Nasal inflammation in sleep apnoea patients using CPAP and effect of heated humidification
Authors: I. Koutsourelakis, E. Vagiakis, E. Perraki, M. Karatza, C. Magkou, M. Kopaka, C. Roussos, S. Zakynthinos
Journal: European Respiratory Journal (2010)

Nasal continuous positive airway pressure (CPAP) can cause undesirable nasal symptoms, such as congestion to obstructive sleep apnoea (OSA) patients, whose symptoms can be attenuated by the addition of heated humidification. However, neither the nature of nasal symptoms nor the effect of heated humidification on nasal pathophysiology and pathology are convincingly known. 20 patients with OSA on nasal CPAP who exhibited symptomatic nasal obstruction were randomised to receive either 3 weeks of CPAP treatment with heated humidification or 3 weeks of CPAP treatment with sham-heated humidification, followed by 3 weeks of the opposite treatment, respectively. Nasal symptom score, nasal resistance, nasal lavage interleukin-6, interleukin-12 and tumour necrosis factor-α and nasal mucosa histopathology were assessed at baseline and after each treatment arm. Heated humidification in comparison with sham-heated humidification was associated with decrease in nasal symptomatology, resistance and lavage cytokines, and attenuation of inflammatory cell infiltration and fibrosis of the nasal mucosa. In conclusion, nasal obstruction of OSA patients on CPAP treatment is inflammatory in origin and the addition of heated humidification decreases nasal resistance and mucosal inflammation.
Effects of a restricted elimination diet on the behaviour of children with attention-deficit hyperactivity disorder (INCA study): a randomised controlled trial
Authors: Lidy M Pelsser, Klaas Frankena, Jan Toorman, Huub F Savelkoul, Anthony E Dubois, Rob Rodrigues Pereira, Ton A Haagen, Nanda N Rommelse, Jan K Buitelaar
Journal: The Lancet (2011)
The Puzzle of Nitrate Tolerance
Authors: Tommaso Gori, John D. Parker
Journal: Circulation (2002)

N itroglycerin (GTN) and other organic nitrates are impor- tant drugs commonly used in cardiovascular medicine, and, more recently, in obstetrics as tocolytic agents. 1 The development of tolerance, ie, the reduction in effect or the requirement for higher doses that appears after continuous use, 2 is a major factor limiting the efficacy of these drugs.Despite their clinical importance in the therapy of ischemic heart disease and heart failure, many aspects of the pharmacology of organic nitrates, including the mechanism(s) of tolerance, remain unclear.In the past decade, studies have demonstrated that organic nitrate therapy leads to complex interactions between the vasculature, neurohormones, and free oxygen radicals.In particular, the concept that GTN treatment causes increased vascular superoxide anion (•O 2 Ϫ ) production, the mechanisms leading to this production, and the consequences of this phenomenon on endothelial function, have all been investigated.In the first part of this 2-part review, these recent findings, as well as the potential role of neurohormonal and autonomic abnormalities, will be described.In the second part, which will appear in the next issue of Circulation, we will propose a new, integrated view on the pathophysiology of nitrate tolerance.
Patient Involvement in Decisions to Limit Treatment: The Crucial Role of Agreement Between Physician and Patient
Authors: Eva C. Winkler, Stella Reiter-Theil, Dorothee Lange-Rieß, Nina Schmahl-Menges, Wolfgang Hiddemann
Journal: Journal of Clinical Oncology (2009)

Purpose The aim of this study was to describe, first, the decision-making process concerning the limitation of life-prolonging treatment (DLT); second, the extent to which patients are actually involved in these decisions; and third, to detect medical and ethical factors that affect patient involvement. Patients and Methods This prospective qualitative study enrolled 76 patients with incurable cancer with whom the limitation of life-prolonging treatment was discussed. Embedded researchers on the wards recorded the patient's history, medical condition, type of treatment limitation discussed, patient wishes, decision-making capacity, and patient involvement using an in-depth documentation procedure. Results While the majority of patients were informed about their diagnosis, therapy, and course of disease (99%, 97%, 90%, respectively), only 47% were involved in DLT. Two thirds of the patients preferred palliative care, and one third wished to extend their lifetime. If patients preferred palliative care, they were more often in line with physicians' treatment goals than patients who were striving for longer survival (91.4% v 46.7%; P = .001). They also were involved significantly more often in DLT. Multivariate analysis showed that age, Karnofsky performance index or decision-making capacity had no impact on patient involvement. Conclusion Only half of the patients were involved in DLT. Surprisingly, the main predictor of patient involvement was not their medical condition, but agreement with physicians' palliative treatment goals. These results show that if physicians switch to comfort care in terminally ill patients and patients are not yet prepared to follow this line, treatment limitations are often decided without involving the patient.
Melanoma cell-derived factors stimulate glycosaminoglycan synthesis by fibroblasts cultured as monolayers and within contracted collagen lattices
Authors: M. Edward
Journal: British Journal of Dermatology (2001)

Background Various tumours exhibit glycosaminoglycan rich, and in particular hyaluronan rich matrices surrounding them that facilitate tumour growth and invasion. In many tumours, this matrix is predominantly synthesized by fibroblasts following stimulation by tumour cell‐derived factors.
Association of atherosclerosis with presence and progression of osteoarthritis: the Rotterdam Study
Authors: Theun Antonius Hoeven, Maryam Kavousi, Stefan Clockaerts, Hanneke J M Kerkhof, Joyce B van Meurs, Oscar Franco, Albert Hofman, Patrick Bindels, Jacqueline Witteman, Sita Bierma-Zeinstra
Journal: Annals of the Rheumatic Diseases (2012)

This study examined whether vascular alterations are associated with the presence and progression of osteoarthritis of the knee, the hip and the different hand joints in a large prospective cohort study.In this population-based study involving participants aged 55 years and older (Rotterdam Study I), men (n=2372) and women (n=3278) were analysed separately. x-Rays of the knee, hip and hand were scored using the Kellgren and Lawrence score for osteoarthritis at baseline, after 6.6 years and 10 years. Measures of atherosclerosis (carotid intima media thickness (IMT) and carotid plaque) and data on covariates (age, body mass index, hypertension, cholesterol ratio, diabetes mellitus and smoking) were collected at baseline. Multivariate logistic regression models with generalised estimated equations were used to calculate OR and corresponding 95% CI. Secondary multiple comparison adjustment resulted in a significance level of p<0.0021.In women, IMT showed an independent association with the prevalence of knee osteoarthritis (adjusted OR (aOR) 1.7, 1.1 to 2.7), and carotid plaque with distal interphalangeal (DIP) osteoarthritis (aOR 1.4, 1.2 to 1.7) and with metacarpophalangeal osteoarthritis (aOR 1.5, 1.1 to 2.2). An independent association for IMT with progression of metacarpophalangeal osteoarthritis was found in women (aOR 2.9, 1.18 to 6.93). Additional adjustment for multiple testing yielded a significant association between carotid plaque and DIP osteoarthritis in women (p<0.001).This study showed independent associations of atherosclerosis with osteoarthritis of the knee and hand joints in women. The evidence was most solid for a relation with DIP osteoarthritis. More research is needed to confirm the associations and examine the differential association with various joints.