tbuckley/cabot-search huggingface dataset:
Effects of Vitaxin on hyperactive osteoclastogenesis in multiple myeloma: A preclinical study.
Authors: L. S. Stucci, M. De Matteo, M. Cives, M. Tucci, F. Silvestris
Journal: Journal of Clinical Oncology (2010)

e18501 Background: Myeloma bone disease (MBD) is characterized by progressive skeleton destruction as effect of accelerated marrow osteoclast (OC) differentiation induced by malignant plasma cells. Myeloma cells, however, exert bone resorptive activity in vitro and OC-like plasma cell polykaryons, are also detectable in vivo in osteolytic lesions. We demonstrated that, similarly to OCs, this property in myeloma cells is dependent on the avb3 integrin, in particular b3 chain, since b3-silenced myeloma cells fail to produce experimental bone erosions. The MoAb Vitaxin (LM609 anti-avb3) was proved to restrain the OC activity in bone metastases from solid tumors. Thus, we explored its effect on bone resorbing malignant plasma cells. Methods: Nine avb3+ myeloma cell lines from patients with MBD were incubated for 48 hr on both calcium phosphate and dentine slices. Five OC preparations from normal macrophages served as controls. Parallel cell preparations were conditioned by Vitaxin and the bone resorption was calculated as both number and area of the erosive pits. Phosphorylation of ERK1/2 induced by avb3 in activated OCs, was also measured by western blot. Results: All myelomas variably produced extensive erosion in vitro whose total value was 10-15% lower than control OCs. However, Vitaxin significantly suppressed this activity. Maximal inhibition was observed by 300 ng/ml which provided the full suppression in four instances whereas a residual activity no higher than 3-5% of the unconditioned controls was revealed in the other myeloma cell lines. Furthermore, in Vitaxin-treated myelomas, phosphorylated ERK1/2 was undetectable by western blot, as in control OCs. Conclusions: By blocking avb3, Vitaxin prevents the ERK1/2 phosphorylation leading to the OC-like activities. Thus, our data suggest that this MoAb is apparently effective in disabling the erosive function of both myeloma cells and OCs in vitro, suggesting its potential use in vivo in future treatments of MBD. No significant financial relationships to disclose.
Uncommon Syndromes and Treatment Manifestations of Malignancy
Authors: Apar Kishor Ganti, Anil Potti, Syed Mehdi
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.21.1.168 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12506187 Uncommon Syndromes and Treatment Manifestations of Malignancy Case 2. Metastatic Non–Small-Cell Lung Cancer Presenting With Leukocytosis Apar Kishor GantixApar Kishor GantiSearch for articles by this author , Anil PottixAnil PottiSearch for articles by this author , Syed MehdixSyed MehdiSearch for articles by this author Show More Department of Internal Medicine, University of North Dakota School of Medicine; and Division of Hematology/Oncology, Veterans’ Affairs Medical Center, Fargo, ND https://doi.org/10.1200/JCO.2003.21.1.168 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease
Authors: Benjamin Lazarus, Yuan Chen, Francis P. Wilson, Yingying Sang, Alex R. Chang, Josef Coresh, Morgan E. Grams
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide and have been linked to acute interstitial nephritis. Less is known about the association between PPI use and chronic kidney disease (CKD). <h3>Objective</h3> To quantify the association between PPI use and incident CKD in a population-based cohort. <h3>Design, Setting, and Participants</h3> In total, 10 482 participants in the Atherosclerosis Risk in Communities study with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m<sup>2</sup>were followed from a baseline visit between February 1, 1996, and January 30, 1999, to December 31, 2011. The data was analyzed from May 2015 to October 2015. The findings were replicated in an administrative cohort of 248 751 patients with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m<sup>2</sup>from the Geisinger Health System. <h3>Exposures</h3> Self-reported PPI use in the Atherosclerosis Risk in Communities study or an outpatient PPI prescription in the Geisinger Health System replication cohort. Histamine<sub>2</sub>(H<sub>2</sub>) receptor antagonist use was considered a negative control and active comparator. <h3>Main Outcomes and Measures</h3> Incident CKD was defined using diagnostic codes at hospital discharge or death in the Atherosclerosis Risk in Communities Study, and by a sustained outpatient estimated glomerular filtration rate of less than 60 mL/min/1.73 m<sup>2</sup>in the Geisinger Health System replication cohort. <h3>Results</h3> Among 10 482 participants in the Atherosclerosis Risk in Communities study, the mean (SD) age was 63.0 (5.6) years, and 43.9% were male. Compared with nonusers, PPI users were more often of white race, obese, and taking antihypertensive medication. Proton pump inhibitor use was associated with incident CKD in unadjusted analysis (hazard ratio [HR], 1.45; 95% CI, 1.11-1.90); in analysis adjusted for demographic, socioeconomic, and clinical variables (HR, 1.50; 95% CI, 1.14-1.96); and in analysis with PPI ever use modeled as a time-varying variable (adjusted HR, 1.35; 95% CI, 1.17-1.55). The association persisted when baseline PPI users were compared directly with H<sub>2</sub>receptor antagonist users (adjusted HR, 1.39; 95% CI, 1.01-1.91) and with propensity score–matched nonusers (HR, 1.76; 95% CI, 1.13-2.74). In the Geisinger Health System replication cohort, PPI use was associated with CKD in all analyses, including a time-varying new-user design (adjusted HR, 1.24; 95% CI, 1.20-1.28). Twice-daily PPI dosing (adjusted HR, 1.46; 95% CI, 1.28-1.67) was associated with a higher risk than once-daily dosing (adjusted HR, 1.15; 95% CI, 1.09-1.21). <h3>Conclusions and Relevance</h3> Proton pump inhibitor use is associated with a higher risk of incident CKD. Future research should evaluate whether limiting PPI use reduces the incidence of CKD.
Clinical benefit of atrasentan for men with metastatic hormone-refractory prostate cancer metastatic to bone
Authors: D. J. Sleep, J. B. Nelson, D. P. Petrylak, J. D. Isaacson, M. A. Carducci
Journal: Journal of Clinical Oncology (2006)

4630 Background: Hormone-refractory prostate cancer (HRPC) metastasizes most commonly to bone. Treatment of advanced HRPC patients focuses on alleviating bone pain that afflicts 85% of patients. New therapies are needed that not only prolong survival but slow the progression of morbidity. Atrasentan, a selective endothelin A receptor antagonist that blocks the effect of endothelin in the bone microenvironment by slowing osteoblast proliferation, may slow disease progression in HRPC patients with bone metastases. Methods: Patients enrolled in a randomized, double-blind, placebo-controlled multinational trial of atrasentan 10 mg with independently confirmed bone metastases (N = 690) were followed until the first event of disease progression, which could be by radiographic (≥2 new lesions on bone scan) or clinical means (eg, pain requiring significant opioids or other interventions, spinal cord compression). Analyses were performed on time to disease progression and separately on time to clinical and radiographic progression. The difference between treatments was analyzed using Kaplan-Meier methods and Cox proportional hazards modeling. Results: N = 335 for placebo; N = 355 for atrasentan. Atrasentan therapy resulted in fewer disease progression events relative to placebo and reduced the risk of disease progression by 19% ( Table ). The differential effect of atrasentan on disease progression was most notable against clinical progression (32% reduction in risk vs placebo). Conclusions: In men with HRPC metastatic to bone, atrasentan delays disease progression, especially clinical events, relative to placebo. [Table: see text] [Table: see text]
Population-Based Mortality Assessment: Baidoa and Afgoi, Somalia, 1992
Journal: JAMA (1993)

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Abstract #LB-247: Walnut consumption decreases mammary gland tumor incidence, multiplicity and growth in the C(3)1Tag transgenic mouse
Authors: Gabriela Ion, Juliana Akinsete, Theadore Witte, Wanda Hardman
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Many scientists now think that diet can alter our risk for developing cancer. Much work is ongoing to identify dietary changes that might reduce risk for cancer. We have reported that consumption of walnuts could reduce breast cancer growth. Walnuts contain multiple ingredients that, individually, have been shown to slow cancer growth including omega 3 fatty acids, antioxidants and phytosterols. We wanted to determine whether regular walnut consumption might also reduce the risk for developing cancer. The walnut content of the diet (18% w/w walnut) was equivalent to a human consumption of 2 servings (2 ounces) per day. Homozygous, male C(3)1 TAg mice were bred with female SV129 mice that were consuming either the control AIN-76 diet or the walnut containing diet. At weaning, the female hemizygous pups were placed on the same diet as the mother. We found that consumption of walnut significantly reduced: tumor incidence (fraction of mice with at least one tumor), the number of glands with tumor and tumor size. Gas chromatography showed that the walnut diet increased the alpha-linolenic acid (omega 3 fatty acid) and decreased the arachidonic acid (omega 6 fatty acid) content of the mammary gland. Gene expression analyses indicated that consumption of the walnut diet altered expression of multiple genes that would be expected to slow proliferation, increase apoptosis and speed differentiation of the mammary epithelial cells. A comparison with another study that had the same omega 3 content as in the walnut diet indicates that the omega 3 content alone could not account for the extent of tumor suppression due to the walnut diet, thus the other components of the walnut also contributed to tumor suppression. The results of this study indicate that walnut consumption could contribute to a healthy diet to reduce risk for breast cancer.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-247.
OP14 Measurement of low density apolipoprotein B associated hepatitis C virus lipoviral particles in genotype 1 infection is more clinically relevant than total viral load
Authors: D Sheridan, S Bridge, D A Sheridan, D Felmlee, H Thomas, S Taylor-Robinson, R Dermot, G Neely, G L Toms, M F Bassendine
Journal: Gut (2010)

Introduction  The density of hepatitis C virus (HCV) in plasma is heterogeneous but the factors that influence this are poorly understood. Evidence from animal models and cell culture suggest that low-density apolipoprotein B (apoB)-associated HCV lipoviral particles (LVP) are more infectious than high density HCV.  Aim  We measured HCV LVP in patients with chronic hepatitis C genotype 1 (CHC-G1) and examined metabolic determinants of LVP load and clinical correlates.  Method  Fasting lipid profiles and HOMA-IR (homeostasis model assessment of insulin resistance) were determined in 51 CHC-G1 patients. LVP and non-LVP viral load were quantitated by real-time RT-PCR of plasma at density d 1.07 g/ml, respectively, following iodixanol density gradient ultracentrifugation. The LVP ratio was calculated using: LVP/(LVP+non-LVP)=LVP ratio.  Results  The mean LVP ratio was 0.241 but varied 25-fold (0.029 to 0.74). When divided above and below the median value of 0.177, those with high LVP ratio had metabolic syndrome characteristics, higher liver stiffness and poorer early virological response rates (EVR) (see Abstract OP14 table 1).  Univariate analysis showed LVP ratio correlated with HOMA-IR (p=.004) and triglyceride (TG)/HDL-C ratio (p=0.004), but not with apoB. In multivariate analysis HOMA-IR was the main determinant of LVP load (log10 IU/ml) (p=0.037; R2=16.6%) but TG/HDL-C ratio was the strongest predictor of LVP ratio (p=0.019; R2=24.4%). Higher LVP ratios were associated with non-response to antiviral therapy (p=0.037) and with greater liver stiffness (p=0.001). There was no association between total viral load and host clinical and metabolic parameters.  Conclusion  Measurement of HCV LVP is of more direct clinical relevance than total HCV viral load. Insulin resistance and associated dyslipidaemia are the major determinants of low-density apoB-associated LVP in fasting plasma. This provides a novel mechanism to explain why insulin resistance is associated with more rapidly progressive liver disease and poorer treatment outcomes.
Preoperative chemotherapy with cisplatin and docetaxel followed by operation and adjuvant radio-chemotherapy in patients with localized gastric or gastro-oesophageal cancer: Results from a phase II feasibility study
Authors: G. Spizzo, A. Devries, G. Steger, J. Zacherl, J. Widder, U. Pluschnig, A. Zabernigg, D. Oefner, R. Stauder, G. Gastl
Journal: Journal of Clinical Oncology (2005)

4226 Background: We performed a phase II feasibility study with neoadjuvant Cisplatin and Docetaxel chemotherapy followed by operation with curative intention and adjuvant radio-chemotherapy in patients with localized gastric or gastro-oesophageal cancer. Methods: Patients were planned to receive 2 to 3 cycles of neoadjuvant chemotherapy with 50 mg/m2 Taxotere and 50 mg/m2 Cisplatin on day 1 of each cycle and were surgically treated within 2 to 4 weeks. To achieve a better reproducibility, clips were set intra-operatively to define the treated area. Patients underwent post-surgical radiotherapy receiving a total dose of 39.6 Gy and 5-FU continuous infusion during radiotherapy. Three chemotherapy cycles of a modified Mayo regime were administered to complete adjuvant therapy. Primary end-points were response-rate and R0-resectability-rate after neoadjuvant chemotherapy. Secondary end-points were tolerability, treatment associated complications, disease-free and overall survival. Results: Fifteen patients were enrolled from beginning of the study in October 2002. The last patient entered the study in December 2004. The median age of the patient sample was 53 years (range 33 - 73). Eleven patients were evaluable for response to preoperative chemotherapy at December 2004. Three patients (27.2%) experienced progressive disease and therefore received a palliative treatment off-study. Three patients (27.2%) presented with stable disease and 5 patients (45.6%) with a partial response after neoadjuvant chemotherapy. In 8 patients (72.7%) a complete resection (R0) was achieved. Serious adverse events were registered in 5 patients including: neutropenia, pulmonary embolism, acute pancreatitis and peri-operative complications (2). Conclusions: Preliminary data show a high response-rate and R0-resectability-rate after a preoperative chemotherapy regime with Cisplatin and Docetaxel. However, due to the high rate of serious adverse events, adaptation and modification of the study protocol is necessary. Results will be updated and presented at the ASCO 2005 meeting. No significant financial relationships to disclose.
Adjuvant chemotherapy for stage II and stage III colon cancer—What is happening in routine practice?
Authors: S. Ananda, S. Kosmider, L. Lim, F. Barnett, J. Desai, P. Gibbs
Journal: Journal of Clinical Oncology (2009)

e15046 Background: Randomised studies have defined adjuvant chemotherapy as standard treatment for stage III colon cancer (SIIICC), with multiple options available. For stage II (SII) disease, the selection of patients for adjuvant treatment remains controversial. There remains limited data on clinician decision making regarding adjuvant chemotherapy in routine clinical practice. Methods: A review of patients treated with SII &amp; IIICC at 4 hospitals, utilising data from BioGrid Australia, where clinician choice and rationale were prospectively documented. Results: 372 patients (37%) with SII and 307 (30%) with SIIICC were identified from 1015 CC patients treated from January 2003 till November 2008. Median age was 68 years, 51% were male; 49% female. 66 (25%) of patients with SIIICC were not offered chemotherapy, predominantly due to advanced age or co-morbidity. Since oxaliplatin and capecitabine became widely available in 2005, 66% of treated patients have received oxaliplatin based therapy, 15% bolus 5-FU alone and 19% capecitabine. For SII disease, overall 81 (26%) pts received adjuvant chemotherapy. Age was the dominant influence on treatment choice with 41% aged 70 (p&lt;0.001) receiving treatment. Patients with high risk features were also more likely to receive adjuvant therapy. (p= 0.006 for those with lymphovascular invasion and p= 0.0068 for those with T4 tumours). Dose reductions and completion rates were similar for SII and III disease, and for older and younger patients. Conclusions: Over 25% of patients with SIIICC do not receive adjuvant chemotherapy in routine practice, with physicians basing non-treatment recommendations predominantly on patient age and co-morbidity. Where treatment is used, oxaliplatin-based therapy is the dominant regimen, except in older patients. In SIICC, adjuvant chemotherapy is used in one in four patients, more frequently in younger patients and those with high risk features. No significant financial relationships to disclose.
Epstein-Barr virus DNA is abundant and monoclonal in the Reed-Sternberg cells of Hodgkin's disease: association with mixed cellularity subtype and Hispanic American ethnicity
Authors: ML Gulley, PA Eagan, L Quintanilla-Martinez, AL Picado, BN Smir, C Childs, CD Dunn, FE Craig, JW Jr Williams, PM Banks
Journal: Blood (1994)
Endobronchial Valves for Emphysema without Interlobar Collateral Ventilation
Authors: Karin Klooster, Nick H.T. ten Hacken, Jorine E. Hartman, Huib A.M. Kerstjens, Eva M. van Rikxoort, Dirk-Jan Slebos
Journal: New England Journal of Medicine (2015)

Bronchoscopic lung-volume reduction with the use of one-way endobronchial valves is a potential treatment for patients with severe emphysema. To date, the benefits have been modest but have been hypothesized to be much larger in patients without interlobar collateral ventilation than in those with collateral ventilation.We randomly assigned patients with severe emphysema and a confirmed absence of collateral ventilation to bronchoscopic endobronchial-valve treatment (EBV group) or to continued standard medical care (control group). Primary outcomes were changes from baseline to 6 months in forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and 6-minute walk distance.Eighty-four patients were recruited, of whom 16 were excluded because they had collateral ventilation (13 patients) or because lobar segments were inaccessible to the endobronchial valves (3 patients). The remaining 68 patients (mean [±SD] age, 59±9 years; 46 were women) were randomly assigned to the EBV group (34 patients) or the control group (34). At baseline, the FEV1 and FVC were 29±7% and 77±18% of the predicted values, respectively, and the 6-minute walk distance was 374±86 m. Intention-to-treat analyses showed significantly greater improvements in the EBV group than in the control group from baseline to 6 months: the increase in FEV1 was greater in the EBV group than in the control group by 140 ml (95% confidence interval [CI], 55 to 225), the increase in FVC was greater by 347 ml (95% CI, 107 to 588), and the increase in the 6-minute walk distance was greater by 74 m (95% CI, 47 to 100) (P<0.01 for all comparisons). By 6 months, 23 serious adverse events had been reported in the EBV group, as compared with 5 in the control group (P<0.001). One patient in the EBV group died. Serious treatment-related adverse events in this group included pneumothorax (18% of patients) and events requiring valve replacement (12%) or removal (15%).Endobronchial-valve treatment significantly improved pulmonary function and exercise capacity in patients with severe emphysema characterized by an absence of interlobar collateral ventilation. (Funded by the Netherlands Organization for Health Research and Development and the University Medical Center Groningen; Netherlands Trial Register number, NTR2876.).
Association Between VDR FokI Polymorphism and Intervertebral Disk Degeneration
Authors: Jian Zhao, Mingyuan Yang, Jie Shao, Yushu Bai, Ming Li
Journal: Genomics Proteomics & Bioinformatics (2015)

Abstract Intervertebral disk degeneration (IDD) is strongly associated with genetic predisposition and environmental susceptibility. Several studies been conducted to investigate the potential association between IDD and FokI polymorphism located in the gene encoding the vitamin D receptor (VDR), and inconsistent conclusions had been reached among different ethnic populations. In order to assess the association between the FokI polymorphism and the risk of IDD, we performed a comprehensive and systematic meta-analysis. Candidate articles were retrieved from PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and China Biology Medical (CBM) with strict inclusion criteria in January 2015. Among the 54 articles that were retrieved, only eight studies met the inclusion criteria. The pooled data analysis based on allele contrast, homozygote, heterozygote, dominant, and recessive models revealed no significant correlation between the FokI polymorphism and the risk of IDD. However, when stratified by ethnicity, significant associations were detected for Hispanics based on allele contrast (OR = 1.395, 95% CI = 1.059–1.836, P = 0.018), homozygote (OR = 1.849, 95% CI = 1.001–3.416, P = 0.049), heterozygote (OR = 1.254, 95% CI = 1.049–1.498, P = 0.013), and dominant (OR = 1.742, 95% CI = 1.174–2.583, P = 0.006) models, and for Asians using the dominant model (OR = 1.293, 95% CI = 1.025–1.632, P = 0.030), whereas there is no significant association detected for Caucasians. In conclusion, FokI polymorphism is not generally associated with IDD, but there is increased risk for IDD in Hispanics and Asians carrying FokI allele T.