tbuckley/cabot-search huggingface dataset:
Production of parathyroid hormone-related peptide in a patient with acute lymphocytic leukemia with extensive osteolytic lesions and hypercalcemia
Authors: Tomoya Miyamura, Fumihiro Taguchi, Hideki Ishikura, Yuji Yufu, Yoshihiro Nishi, Sayuri Yamashita, Junji Nishimura, Hajime Nawata
Journal: American Journal of Hematology (1995)
Of rice and men: Bill Kelley's next generation
Authors: E. W. Holmes
Journal: Journal of Clinical Investigation (2005)

I first met Bill Kelley in 1970 when I applied for a fellowship in his laboratory at Duke. I had the feeling in this first meeting that this was a man who could have a significant impact on my life. Thinking back 35 years now, I know that he did and I suspect that he had a similar influence on many in the Association of American Physicians.
Integration of Multislice Computed Tomography With Magnetic Navigation Facilitates Percutaneous Coronary Interventions Without Additional Contrast Agents
Authors: Francesca Pugliese, Steve Ramcharitar, Carl Schultz, Jurgen Ligthart, Pim de Feyter, Huling Li, Nico Mollet, Martin van de Ent, Patrick W. Serruys, Robert Jan van Geuns
Journal: Journal of the American College of Cardiology (2009)
Bombesin Regulates Cyclin D1 Expression through the Early Growth Response Protein Egr-1 in Prostate Cancer Cells
Authors: Dongmei Xiao, Dharmaraj Chinnappan, Richard Pestell, Christopher Albanese, Horst Christian Weber
Journal: Cancer Research (2005)

Abstract Our previous studies indicate that the activation of mitogen-activated protein kinase (MAPK) pathway is involved in bombesin-induced cell proliferation in prostate cancer cells. Cyclin D1 is a critical regulator involved in cell cycle progression through the G1 phase into the S phase, thereby contributing to cell proliferation. Mostly, mitogen-stimulated expression of cyclin D1 is attributed to the extracellular signal-regulated kinase (ERK) activation. Here, we found that bombesin induced human cyclin D1 expression on both mRNA and protein levels in DU-145 prostate cancer cells. Mutational analyses showed that bombesin-enhanced cyclin D1 transcription required the binding of nuclear proteins to the −143 to −105 region of the human cyclin D1 promoter, which contains binding sites for transcription factors Sp-1 and early growth response protein (Egr-1). Do novo protein synthesis was requisite for bombesin-induced cyclin D1 expression. Further studies showed Egr-1 was induced upon bombesin stimulation. The induction of Egr-1 expression and its binding to the cyclin D1 promoter were essential for bombesin-enhanced cyclin D1 transcription. Inhibition of MAPK pathway with either the MEK1 inhibitor PD98059 or a dominant-negative Ras mutant, RasN17, abolished bombesin-induced cyclin D1 activation. Taken together, bombesin-induced cyclin D1 expression in prostate cancer cells is mediated by Egr-1 activation and the interaction of Egr-1 with the Egr-1/Sp1 motif of the cyclin D1 promoter through the activation of MAPK pathway. These findings represent a novel mechanism of bombesin-dependent stimulation of mitogenesis by regulating directly the cell cycle in prostate cancer.
The correlation of RANK, RANKL and TNFα expression with bone loss volume and polyethylene wear debris around hip implants
Authors: Christopher A. Holding, David M. Findlay, Roumen Stamenkov, Susan D. Neale, Helen Lucas, A.S.S.K. Dharmapatni, Stuart A. Callary, Kush R. Shrestha, Gerald J. Atkins, Donald W. Howie, David R. Haynes
Journal: Biomaterials (2006)
Unexpected Immunohistochemical Localization of Deoxycytidine Kinase
Authors: Lorelei Johnson, Raymond Lai, Cheryl Santos, Laith Dabbagh, John Mackey
Journal: Clinical Cancer Research (2006)

To the Editor: 

We read with great interest the April 15, 2006 article by Sebastiani et al. reporting immunohistochemical evaluation of deoxycytidine kinase (dCK) in 44 pancreatic cancer patients, which found that most cases (40 of 44) were positive for dCK ([1][1]). Based on the observed staining
Prognostic Importance of Preoperative CA-125 in International Federation of Gynecology and Obstetrics Stage I Epithelial Ovarian Cancer: An Australian Multicenter Study
Authors: Sellva Paramasivam, Lee Tripcony, Alex Crandon, Micheal Quinn, Ian Hammond, Donald Marsden, Anthony Proietto, Margaret Davy, Jonathan Carter, James Nicklin, Lewis Perrin, Andreas Obermair
Journal: Journal of Clinical Oncology (2005)

To evaluate the prognostic significance of preoperative CA-125 levels on overall survival of patients with International Federation of Gynecology and Obstetrics (FIGO) stage I epithelial ovarian cancer (EOC).Data from 518 patients with FIGO stage I EOC treated in seven gynecologic oncology centers throughout Australia between 1990 and 2002 were analyzed. Patients with borderline tumors and nonepithelial ovarian carcinomas were excluded, as were women in whom CA-125 had not been determined preoperatively. Preoperative CA-125 levels were studied in surgically staged and incompletely staged patients and compared with prognostic factors, such as substage, grade, and histologic type. Multivariate Cox models were calculated.CA-125 levels more than 30 U/mL were associated with higher grade, substage 1B and 1C, nonmucinous histologic type, and older age. In univariate analysis, higher histologic grade, the absence of surgical staging, and preoperative CA-125 levels more than 30 U/mL were associated with impaired survival. Multivariate analysis identified histologic grade, preoperative CA-125, and surgical staging as independent predictors for survival. In the subgroup of completely surgically staged patients, the 5-year overall survival rate was 82% (95% CI, 76% to 88%) for patients with CA-125 levels more than 30 U/mL and 95% (95% CI, 90% to 99%) for patients with CA-125 levels of 30 U/mL or less (P = .028). In the group of incompletely staged patients, the 5-year survival rates were similar for patients with elevated and normal serum CA-125 levels.Complete surgical staging, histologic grade, and preoperative serum CA-125 levels are independent prognostic factors and should be included in the decision making for chemotherapy.
SU5416 and SU5614 inhibit kinase activity of wild-type and mutant FLT3 receptor tyrosine kinase
Authors: Kevin W. H. Yee, Anne Marie O'Farrell, Beverly D. Smolich, Julie M. Cherrington, Gerald McMahon, Cecily L. Wait, Laura S. McGreevey, Diana J. Griffith, Michael C. Heinrich
Journal: Blood (2002)
The Functional Impact of SLC6 Transporter Genetic Variation
Authors: Maureen K. Hahn, Randy D. Blakely
Journal: The Annual Review of Pharmacology and Toxicology (2006)

Solute carrier 6 (SLC6) is a gene family of ion-coupled plasma membrane cotransporters, including transporters of neurotransmitters, amino acids, and osmolytes that mediate the movement of their substrates into cells to facilitate or regulate synaptic transmission, neurotransmitter recycling, metabolic function, and fluid homeostasis. Polymorphisms in transporter genes may influence expression and activity of transporters and contribute to behavior, traits, and disease. Determining the relationship between the monoamine transporters and complex psychiatric disorders has been a particular challenge that is being met by evolving approaches. Elucidating the functional consequences of and interactions among polymorphic sites is advancing our understanding of this relationship. Examining the influence of environmental influences, especially early-life events, has helped bridge the gap between genotype and phenotype. Refining phenotypes, through assessment of endophenotypes, specific behavioral tasks, medication response, and brain network properties has also improved detection of the impact of genetic variation on complex behavior and disease.
Effectiveness of Sirolimus-Eluting Stent Implantation for the Treatment of Ostial Left Anterior Descending Artery Stenosis With Intravascular Ultrasound Guidance
Authors: Ki-Bae Seung, Young-Hak Kim, Duk-Woo Park, Bong-Ki Lee, Cheol Whan Lee, Myeong-Ki Hong, Pum-Joon Kim, Wook-Sung Chung, Seung-Jea Tahk, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2005)
Pragmatic prognostic approach of rheumatoid arthritis-associated interstitial lung disease
Authors: V. Cottin
Journal: European Respiratory Journal (2010)

Rheumatoid arthritis (RA) affects approximately 1% of the adult population, with female predominance. Pulmonary involvement is common, and may include a variety of manifestations namely RA-associated interstitial lung disease (ILD) 1, 2, pleural disease 3, rheumatoid nodules and airway complications (crico-arytenoid arthritis, bronchiectasis, bronchiolitis 4). ILD is usually detected in patients already diagnosed with RA (mostly between the ages of 50 and 60 yrs and more commonly in males), but isolated pulmonary disease may precede the onset of articular disease. Clinically significant RA-ILD affects approximately 7% of patients with RA 5, whereas a higher prevalence was found by autopsy studies or prospective screening studies using high-resolution chest tomography (HRCT) 1. Thus, RA-ILD may affect up to one out of 1,000 adult persons in the general population. When present, it may decrease the survival of patients by 3.5 to 4.9 yrs 6, although the outcome is highly variable, with indolent course and conversely rapid deterioration being reported. Tobacco smoking, a potentially reversible risk factor, increases the incidence and severity of RA 7 through a proposed mechanism of epitope citrullination in a predisposing genetic background 8, increases the risk of severe extra-articular manifestations of RA 5 and might increase the risk of having ILD in patients with RA although conflicting results have been reported 1, 9.

Much of the complexity of interstitial pneumonia arises from the lack of a definite relationship between histopathological and imaging phenotypes. The currently available data indicate that the histopathological pattern of usual interstitial pneumonia (UIP) may be equally as frequent as non-specific interstitial pneumonia (NSIP) in patients with RA-ILD 10, contrasting with the predominance of NSIP in the other connective tissue diseases. Patterns of organising pneumonia, lymphocytic interstitial pneumonia, diffuse alveolar damage, and even desquamative …
Phase III Trial of Epirubicin Plus Paclitaxel Compared With Epirubicin Plus Cyclophosphamide As First-Line Chemotherapy for Metastatic Breast Cancer: United Kingdom National Cancer Research Institute Trial AB01
Authors: Ruth E. Langley, James Carmichael, Alison L. Jones, David A. Cameron, Wendi Qian, Barbara Uscinska, Anthony Howell, Mahesh Parmar
Journal: Journal of Clinical Oncology (2005)

To compare the effectiveness and tolerability of epirubicin and paclitaxel (EP) with epirubicin and cyclophosphamide (EC) as first-line chemotherapy for metastatic breast cancer (MBC).Patients previously untreated with chemotherapy (except for adjuvant therapy) were randomly assigned to receive either EP (epirubicin 75 mg/m2 and paclitaxel 200 mg/m2) or EC (epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2) administered intravenously every 3 weeks for a maximum of six cycles. The primary outcome was progression-free survival; secondary outcome measures were overall survival, response rates, and toxicity.Between 1996 and 1999, 705 patients (353 EP patients and 352 EC patients) underwent random assignment. Patient characteristics were well matched between the two groups, and 71% of patients received six cycles of treatment. Objective response rates were 65% for the EP group and 55% for the EC group (P = .015). At the time of analysis, 641 patients (91%) had died. Median progression-free survival time was 7.0 months for the EP group and 7.1 months for the EC group (hazard ratio = 1.07; 95% CI, 0.92 to 1.24; P = .41), and median overall survival time was 13 months for the EP group and 14 months for the EC group (hazard ratio = 1.02; 95% CI, 0.87 to 1.19; P = .8). EP patients, compared with EC patients, had more grade 3 and 4 mucositis (6% v 2%, respectively; P = .0006) and grade 3 and 4 neurotoxicity (5% v 1%, respectively; P < .0001).In terms of progression-free survival and overall survival, there was no evidence of a difference between EP and EC. The data demonstrate no additional advantage to using EP instead of EC as first-line chemotherapy for MBC in taxane-naïve patients.
Polymorphic Hh genes in the HLA-B(C) region control natural killer cell frequency and activity.
Authors: D P Dubey, C A Alper, N M Mirza, Z Awdeh, E J Yunis
Journal: The Journal of Experimental Medicine (1994)

We demonstrated earlier that individuals homozygous for conserved major histocompatibility complex (MHC)-extended haplotypes have low natural killer (NK) activity as measured by cytolysis of the K562 tumor cell lines. In the present study, we investigated the segregation and MHC linkage of NK activity in families in which MHC haplotypes of human histocompatibility leukocyte antigens (HLA)-A, -C, and -B, complotype, and DR specificities are known. In two informative families, low activity was inherited as a recessive trait linked to the MHC. By using individuals homozygous for specific fragments of extended haplotypes or for HLA-B alleles, we found that the HLA-C and -B and not the complotype or HLA-DR region contains genes controlling NK activity. The majority of the unrelated individuals with low NK activity were homozygous or doubly heterozygous for HLA-B7 (Cw7), B8 (Cw7), B44 (Cw5), B18, or B57 (Cw6). Thus, these alleles form one complementation group designated NKB1. Another less frequent group, NKB2, was also identified, and consisted of individuals homozygous for B35 (Cw4). NK activity was correlated with the number of circulating NK (CD16+ CD56+) cells. Individuals homozygous for the NKB complementation groups have fewer circulating NK cells than individuals heterozygous for these alleles and alleles of other complementation groups, possibly explaining the low activity of cells in these subjects. These findings suggest that during the maturation of NK cells there is NK cellular deletion in donors homozygous for NKB genes resulting in low NK cell numbers and activity.
BRAF Mutation in Papillary Thyroid Cancer: Pathogenic Role, Molecular Bases, and Clinical Implications
Authors: Mingzhao Xing
Journal: Endocrine Reviews (2007)

In recent years, the T1799A B-type Raf kinase (BRAF) mutation in thyroid cancer has received enthusiastic investigation, and significant progress has been made toward understanding its tumorigenic role and clinical significance. Among various thyroid tumors, this mutation occurs uniquely in papillary thyroid cancer (PTC), the most common endocrine malignancy, and some apparently PTC-derived anaplastic thyroid cancers. Many studies have found this mutation to be associated with those clinicopathological characteristics of PTC that are conventionally known to predict tumor progression and recurrence, including, for example, old patient age, extrathyroidal invasion, lymph node metastasis, and advanced tumor stages. Direct association of BRAF mutation with the clinical progression, recurrence, and treatment failure of PTC has also been demonstrated. The BRAF mutation has even been correlated with PTC recurrence in patients with conventionally low-risk clinicopathological factors. Some molecular mechanisms determining BRAF mutation-promoted progression and the aggressiveness of PTC have recently been uncovered. These include the down-regulation of major tumor suppressor genes and thyroid iodide-metabolizing genes and the up-regulation of cancer-promoting molecules, such as vascular endothelial growth factor, matrix metalloproteinases, nuclear transcription factor κB, and c-Met. Thus, BRAF mutation represents a novel indicator of the progression and aggressiveness of PTC. Significant advances have also occurred in the preclinical testing of new therapeutic strategies targeting the MAPK pathway aberrantly activated by BRAF mutation and other related mutations. New mitogen extracellular kinase (MEK) inhibitors developed recently are particularly promising therapeutic agents for thyroid cancer. With these advances, it has become clearer that BRAF mutation will likely have significant impact on the clinical management of PTC.
Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911)
Authors: Michel Bolla, Hein van Poppel, Laurence Collette, Paul van Cangh, Kris Vekemans, Luigi Da Pozzo, Theo M de Reijke, Antony Verbaeys, Jean-François Bosset, Roland van Velthoven, Jean-Marie Maréchal, Pierre Scalliet, Karin Haustermans, Marianne Piérart
Journal: The Lancet (2005)
Clinical Features of Acute Coronary Syndromes in Patients With Human Immunodeficiency Virus Infection
Authors: Priscilla Y. Hsue, Kamini Giri, Sara Erickson, John S. MacGregor, Naji Younes, Amandeep Shergill, David D. Waters
Journal: Circulation (2004)

Patients with HIV infection exhibit increased rates of coronary events; however, the clinical features of acute coronary syndromes (ACS) in HIV-infected patients have not been well defined.Between 1993 and 2003, 68 HIV-infected patients were hospitalized with ACS. We compared the clinical features and outcome of these patients with those of 68 randomly selected control patients with ACS without HIV. HIV patients were on average more than a decade younger than controls and more likely to be male and current smokers and to have low HDL cholesterol. They were less likely than controls to have diabetes or hyperlipidemia, and their TIMI (Thrombolysis In Myocardial Infarction) risk scores on admission were significantly lower. At coronary angiography, the number of vessels with >50% stenosis was 1.3+/-1.0 in HIV patients and 1.9+/-1.2 in controls (P=0.007). Restenosis developed in 15 of 29 HIV patients who underwent percutaneous coronary intervention compared with 3 of 21 controls (52% versus 14%, P=0.006).HIV patients with ACS are younger and more likely to be males and current smokers and to have low HDL cholesterol levels compared with other ACS patients. Their TIMI risk scores are lower, and they are more likely to have single-vessel disease; however, their restenosis rates after percutaneous coronary intervention are unexpectedly high.
Alpha granule proteins in type I von Willebrand's disease
Authors: Laurie P. McKeown, Sybil B. Williams, Brenda Shafer, Natalie Murray, Harvey R. Gralnick
Journal: American Journal of Hematology (1993)

Platelet von Willebrand factor (vWf) is located in the alpha granules. Individuals with type I von Willebrand's disease (vWd) with prolonged bleeding times are best discriminated from those who have normal bleeding times by the normal level of platelet vWf ristocetin cofactor activity (vWf activity) and, to a lesser extent, by their platelet vWf antigen content. We have studied the content of adhesive proteins and platelet factor-4 (PF-4), and beta-thromboglobulin (beta TG) in the platelet alpha granules of types I and III vWd patients to determine if other alterations in alpha granule contents of proteins occur in vWd. We found that type I vWd patients with prolonged or normal bleeding times could not be differentiated on the basis of their platelet levels of beta TG, PF-4, fibronectin, or fibrinogen. The levels of the alpha granule constituents in the type I vWd patient were similar to normal except for the platelet fibrinogen concentration. Patients with type I vWd, regardless of the level of platelet vWf activity of antigen, had increased levels of platelet fibrinogen. The patients with type III vWd who had undetectable levels of platelet and plasma vWf also had increased levels of platelet fibrinogen. In our study we could not attribute the variation in the platelet vWf activity and antigen in type I vWd to the size of the alpha granule pool as determined by the measurement of other alpha granule proteins. The mechanism(s) of increased platelet fibrinogen in these vWd patients is at present unknown.
A Preclinical Model of CD38-Pretargeted Radioimmunotherapy for Plasma Cell Malignancies
Authors: Damian J. Green, Nural N. Orgun, Jon C. Jones, Mark D. Hylarides, John M. Pagel, Donald K. Hamlin, D.S. Wilbur, Yukang Lin, Darrell R. Fisher, Aimee L. Kenoyer, Shani L. Frayo, Ajay K. Gopal, Johnnie J. Orozco, Theodore A. Gooley, Brent L. Wood, William I. Bensinger, Oliver W. Press
Journal: Cancer Research (2013)

The vast majority of patients with plasma cell neoplasms die of progressive disease despite high response rates to novel agents. Malignant plasma cells are very radiosensitive, but the potential role of radioimmunotherapy (RIT) in the management of plasmacytomas and multiple myeloma has undergone only limited evaluation. Furthermore, CD38 has not been explored as a RIT target despite its uniform high expression on malignant plasma cells. In this report, both conventional RIT (directly radiolabeled antibody) and streptavidin-biotin pretargeted RIT (PRIT) directed against the CD38 antigen were assessed as approaches to deliver radiation doses sufficient for multiple myeloma cell eradication. PRIT demonstrated biodistributions that were markedly superior to conventional RIT. Tumor-to-blood ratios as high as 638:1 were seen 24 hours after PRIT, whereas ratios never exceeded 1:1 with conventional RIT. (90)Yttrium absorbed dose estimates demonstrated excellent target-to-normal organ ratios (6:1 for the kidney, lung, liver; 10:1 for the whole body). Objective remissions were observed within 7 days in 100% of the mice treated with doses ranging from 800 to 1,200 μCi of anti-CD38 pretargeted (90)Y-DOTA-biotin, including 100% complete remissions (no detectable tumor in treated mice compared with tumors that were 2,982% ± 2,834% of initial tumor volume in control animals) by day 23. Furthermore, 100% of animals bearing NCI-H929 multiple myeloma tumor xenografts treated with 800 μCi of anti-CD38 pretargeted (90)Y-DOTA-biotin achieved long-term myeloma-free survival (>70 days) compared with none (0%) of the control animals.
Pemetrexed in combination with oxaliplatin as a first-line therapy for advanced gastric cancer: a multi-institutional phase II study
Authors: L. Celio, C.N. Sternberg, R. Labianca, I. La Torre, V. Amoroso, C. Barone, G. Pinotti, S. Cascinu, F. Di Costanzo, G.L. Cetto, E. Bajetta
Journal: Annals of Oncology (2009)
Wasp venom immunotherapy expands a subpopulation of CD4+CD25+ forkhead box protein 3–positive regulatory T cells expressing the T-cell receptor Vβ2 and Vβ5.1 chains
Authors: Andreas Kerstan, Niklas Beyersdorf, Johanna Stoevesandt, Axel Trautmann
Journal: Journal of Allergy and Clinical Immunology (2012)