tbuckley/cabot-search huggingface dataset:
Risk of renal dysfunction with zoledronic acid in patients with metastatic solid tumors
Authors: K. Barot, S. Wu, X. Zhu
Journal: Journal of Clinical Oncology (2008)

20530 Background: Zoledronic acid is a bisphosphonate used extensively in patients with metastatic bone disease to reduce skeletal related events. It is associated with renal toxicity but its contribution to renal dysfunction is not clear. This meta-analysis was conducted to determine the risk of developing renal dysfunction among solid tumor patients with bone metastasis receiving the standard treatment of zoledronic acid. Methods: Databases from Pubmed, Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies. Eligible studies were prospective randomized placebo-controlled clinical trials using zoledronic acid at the standard dose of 4 mg over 15 minutes IV infusion with available data for analysis. The summary incidence rate and relative risk were calculated using the random-effects model or the fixed-effects model based on the heterogeneity of the included studies. Results: A total of 2,015 patients from 7 clinical trials with solid tumors (breast cancer, prostate and other solid tumors) with bone metastasis were included for analysis. The summary overall incidences of all-grade and high-grade (i.e. grade 3–4) renal dysfunction were 9.0% (95% CI: 5.7–13.9%) and 1.4% (95% CI: 0.5–4.0%) respectively. For patients with breast cancer, the summary incidence of renal dysfunction was 6.2% (95% CI: 5.0–7.8%); while for patients with prostate cancer, the summary incidence was 13.6% (95% CI: 7.6–23.2%). Zoledronic acid was found to contribute to the development of renal dysfunction significantly in comparison with placebo controls with a relative risk of 1.39 (95% CI: 1.02–1.88; P = 0.037). The risk may vary in patients with abnormal baseline creatinine (RR 1.95, 95% CI: 0.54–7.02, p = 0.30). Conclusions: There is a significant risk of developing renal dysfunction in solid tumor patients with bone metastasis. The risk may vary with tumor type and base line renal function. Adequate monitoring and treatment is recommended to minimize the risks. No significant financial relationships to disclose.
Randomized phase II study of human anti-platelet-derived growth factor receptor alpha (PDGFRα) monoclonal antibody (IMC-3G3) with paclitaxel/carboplatin (P/C) or P/C alone in first-line treatment of stage IIIb/IV non-small cell lung cancer (NSCLC).
Authors: D. E. Gerber, R. A. Brekken, T. Hoang, H. Youssoufian, E. K. Rowinsky, N. Loizos, G. D. Shah
Journal: Journal of Clinical Oncology (2010)

TPS296 Background: This study, scheduled to begin enrollment in January 2010, will evaluate P/C alone or with IMC-3G3 in first- line treatment of stage IIIB/IV NSCLC. IMC-3G3 is an IgG1-type recombinant human monoclonal antibody that binds PDGFRα with high affinity, blocks ligand-induced cell mitogenesis and receptor autophosphorylation, and inhibits ligand-induced receptor autophosphorylation of the downstream signaling molecules Akt and MAP kinase (Mol Cancer Ther 2005;4:369). PDGFRα is expressed on 51% of lung cancers (ImClone Systems, data on file). Tumor expression of PDGF ligands correlates with stromal fibroblast infiltration into lung tumors, suggesting the presence of paracrine mechanisms of tumor growth involving stromal-expressed PDGFRα (Clin Cancer Res 2006;12:2676). The PDGF/PDGFRα signaling axis contributes to the proliferation, growth and invasiveness of a variety of cancers in vivo and in vitro (Science1988;241:1346, Proc Natl Acad Sci USA 1993;90:393, Mol Cancer Ther 2007;6:1932), and abrogation of this axis leads to tumor growth inhibition in vivo (Mol Cancer Ther 2005;4:369). Phase I studies of IMC-3G3 monotherapy demonstrated a favorable safety and tolerability profile. Methods: Enrollment of 136 patients previously untreated for stage IIIB (with effusion)/IV NSCLC will occur at 20-25 centers in the United States. Efficacy and safety will be assessed, with progression-free survival as the primary endpoint. Potential associations between clinical outcomes and tumor PDGFRα expression and serum vascular endothelial growth factor (VEGF)/PDGF levels, and the relationship between IMC-3G3 treatment and serum VEGF/PDGF levels will be assessed. Patients will be randomized to receive IMC-3G3 (15 mg/kg) on Days 1 and 8 with paclitaxel (200 mg/m2) and carboplatin (AUC=6) on Day 1 of 21-day cycles (Arm A), or chemotherapy alone (Arm B) for 4 to 6 cycles (followed by IMC-3G3 alone in Arm A) in the absence of disease progression or other withdrawal criteria. Upon disease progression, patients in Arm B may receive IMC-3G3 monotherapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImClone Systems ImClone Systems
Leprosy To-day
Authors: H B HEWITT, T R MUNRO
Journal: BMJ (1964)

MEDICLJOURNALseverely atherosclerotic and thrombosed.It is of interest that Atromid given to rabbits with induced atheroma lowers the level of cholesterol in the serum, but has no effect on either fibrous or fatty aortic lesions.'7Studies of the effect of the non-ionic detergents (Tweens and Tritons) on atheroma induced in animals with cholesterol show that these compounds increase the capacity of the plasma to bind lipid and prevent the formation of atheroma.1820 However, these same compounds may cause lipid to be deposited in the renal tubule'9 and reticulo- endothelial system. 19 2They also provoke spontaneous atherosclerosis in the dog.21Hence they are probably both unsuitable and too dangerous for use in man.The detergent or surface-active properties of phospho-lipids23 disperse cholesterol and other hydrophobic lipids in the cell24 and appear to displace cholesterol and triglycerides from the tissue into the plasma.2'Thus, phospholipid mobilizes cholesterol,'3 stabilizes the suspension of cholesterol in the blood,26 and reduces the amount of lipid deposited in the aortas of rabbits with atheroma produced by a diet rich in cholesterol.27Furthermore, the macrophages28 and other cells in the arterial wall29 respond to infiltration with cholesterol by synthesizing phospholipid-presumably in an attempt to disperse it.It is tempting to speculate whether infusion of phospholipid may eventually prove to be of some value in human atherosclerosis, but at present too little is known about its effects on arteries and other tissues.
Prevalence of bronchiectasis on chest computed tomography in young patients with cystic fibrosis using two different image analysis strategies
Authors: Wieying Kuo, Aukje Bos, Stephen Stick, Harm Tiddens
Journal: European Respiratory Journal (2013)

Background: Presence of bronchiectasis (BE) on chest Computed Tomography (CT) in young children with cystic fibrosis (CF) is an essential outcome measure since these patients have high risk of progressive lung disease. It is important to develop objective, sensitive and reproducible methods to detect and monitor BE in the young CF population.

Aims: To compare the sensitivity of 2 methods to quantify BE on chest CTs of young CF patients.

Methods: 10 chest CTs of patients aged 2 years were randomly selected from the Sophia Children’s Hospital and 10 patients aged 3 years from the Princess Margaret Hospital for Children. Follow up chest CT of all patients 2 years later (age 4 and 5 years) were analyzed. CTs were randomized and de-identified (Myrian, Intrasense, France). BE was scored with the CF-CT scoring module. The airway-artery (AA) pairs on the CTs were also counted and scored in every airway generation. BE was defined as an AA-ratio> 1.

Results: No significant difference in incidence of BE was found between the 2 cohorts. CF-CT scoring: 1st CT, 11 patients with BE (55%); 2nd CT, 13 patients with BE (65%). AA>1: 1st CT 3 patients with BE (15%); 2nd CT, 10 patients with BE (50%).

Conclusion: This study supports the prevalence and progressive nature of BE in young CF patients as observed in previous studies. The AA method underestimates the prevalence of BE relative to CF-CT scoring in patients age 2-3 years. CF-CT scoring is more sensitive to detect BE since the abnormal airways not accompanied by visible arteries are included for analysis in contrary to the AA analysis. Adaptations of the AA method are being tested.

Grants: NCFS.
Comparison of mammography, sonography and MRI in patients receiving neoadjuvant chemotherapy for breast cancer: Final results of a prospective study
Authors: C. Andreetta, S. Russo, V. Londero, M. Mansutti, A. Minisini, G. Cardellino, F. Valent, C. Zuiani, M. Bazzocchi, F. Puglisi
Journal: Journal of Clinical Oncology (2006)

10538 Background: Imaging techniques used to evaluate response during neoadjuvant chemotherapy for breast cancer include mammography (Mx), sonography (US) and MRI. This study prospectively evaluated the ability of each technique to determine pathologic response in breast cancer patients undergoing neoadjuvant chemotherapy. Methods: Forty women with operable breast cancer (T ≥ 2 cm, N0–1, M0) were treated with four cycles of anthracycline-based and taxane-based neoadjuvant chemotherapy as part of a phase II clinical trial. The longest diameter of each tumor (n = 48 neoplastic foci) was measured by Mx, US and MRI at baseline, after two cycles and after 4 cycles of chemotherapy, before surgery. Tumor size at pathology was determined and considered as gold standard of response. Differences among techniques in measuring tumor diameters were evaluated by means of t-test. Results: At baseline, US provided statistically higher measures than Mx (mean difference: 6.3 mm, p &lt; 0.0001) or MRI (mean difference: 5.6 mm, p &lt; 0.0001). No difference was observed between Mx and MRI (mean difference: 0.59 mm, p = 0.5). After two cycles of chemotherapy, tumor diameter measured by US was significantly longer than that measured by Mx (mean difference: 8.8 mm, p &lt; 0.0001) and significantly shorter than that measured by MRI (mean difference: −5.1 mm, p = 0.0009). Mx provided longer measures than MRI (mean difference: 4.4 mm, p = 0.0034). After four cycles of chemotherapy, US provided significantly shorter measures than Mx (mean difference: 11.8 mm, p &lt; 0.0001) and MRI (mean difference: −3.3 mm, p = 0.007), whereas tumor size measured by Mx was significantly longer than that measured by MRI (mean difference: 6.75 mm, p = 0.0027). In addition, the tumor diameter measured by the pathologist was longer than that measured by US (mean difference: 2.6 mm, p = 0.09) and significantly shorter than that measured by Mx (mean difference: −7.8 mm, p &lt; 0.0001). No statistically significant difference was observed between MRI and pathological measures (mean difference: −1.0, p = 0.5). Conclusions: This study provides further evidence that, among imaging techniques, MRI is the best method to evaluate the tumor size after neoadjuvant chemotherapy for breast cancer. No significant financial relationships to disclose.
A phase I dose-escalation study of SCH 900776, a selective inhibitor of checkpoint kinase 1 (CHK1), in combination with gemcitabine (Gem) in subjects with advanced solid tumors.
Authors: A. Daud, G. M. Springett, D. S. Mendelson, P. N. Munster, J. W. Goldman, J. R. Strosberg, G. Kato, T. Nesheiwat, R. Isaacs, L. S. Rosen
Journal: Journal of Clinical Oncology (2010)

3064 Background: In cells undergoing DNA synthesis,antimetabolite-induced replication arrest results in the induction of CHK1, halting the progression of cells through G1/S to allow for DNA damage repair. Inhibition of CHK1 by SCH 900776 is hypothesized to synergize with Gem to promote replication fork collapse and apoptosis, even in the setting of anti-metabolite resistance. Methods: A dose escalation study of SCH 900776 alone and in combination with fixed doses of Gem was conducted in subjects with advanced solid tumors. Subjects were assessed for safety, tolerability, dose-limiting toxicity (DLT), and maximal administered dose (MAD). A recommended phase II dose (RP2D) was determined based on the safety profile at pharmacologically active exposures. Results: Twenty-six subjects have been enrolled and treated with 10 (n=3), 20 (n=3), 40 (n=7), 80 (n=6), and 112 mg/m2 (n=7) of SCH 900776 administered alone and following Gem (800 mg/m2) on days 1 and 8 every 21 days. No SAEs or DLTs have been observed during SCH 900776 monotherapy lead-in. Three reversible DLTs have been observed for the combination; supraventricular tachycardia with pneumonia/pneumonitis at 40 mg/m2 and atrial fibrillation and grade 4 thrombocytopenia at 112 mg/m2 (1 subject each) of SCH 900776. MAD is 112 mg/m2. Clinical activity has been noted in 4 subjects: PR in melanoma, prolonged SD in spindle cell sarcoma, and SD in pancreatic cancer and cholangiocarcinoma previously treated with Gem. Mean t1/2 is 6.29-9.38 hrs. Cmax and AUC(I) increase dose-proportionally across the dose range of SCH 900776. Similar PK exposures exist between SCH 900776 monotherapy and in combination with Gem. Exposure threshold for preclinical activity (>0.5uM Cmax) and PD evidence of target engagement were achieved in the first dose cohort (10 mg/m2). Conclusions: Pharmacologically active plasma concentrations of SCH 900776 associated with the modulation of the CHK1 mechanism have been safely achieved in combination with Gem with early evidence of clinical activity, including in tumors previously progressing on Gem. Dose-related biomarker correlation and RP2D will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Research Laboratories Merck Research Laboratories Merck Research Laboratories Merck Research Laboratories
P0103 : “Pinro” hypothesis for the pathophysiological mechanism about Hepatitis B Virus (HBV) related Acute-on-Chronic Liver Failure (ACLF) Patients - The crucial role of Submassive Hepatic Necrosis (SMHN)
Authors: B. Zeng, L.-Y. Chen, N.-N. Zhang, S. Yin, S.-T. Li, H.-L. Weng, Q. Xia, T.-L. Wang, H. Li
Journal: Journal of Hepatology (2015)
他汀时代的烟酸：有作用吗？我们疑虑什么？
Authors: 严晓伟
Journal: BMJ (2007)

他汀类药物是一类治疗高胆固醇血症的有效药物。大量临床研究显示这类药物用于心血管病高危人群可以显著降低患病率和病死率，因此在目前的脂质代谢异常和动脉粥样硬化（AS）疾病治疗指南中被广泛推荐。近年来一系列的大规模临床研究显示了积极降低低密度脂蛋白胆固醇（LDL—C）的治疗在心血管病患者降低临床事件的有效性。目前的治疗指南将LDL—C作为调脂治疗的首要目标。在心血管病极高危患者，甚至可以选择性地将LDL—C降低至1．81mmol／L（70mg／dl）以下。尽管如此，研究发现在高密度脂蛋白胆固醇（HDL—C）显著降低的患者，他汀类药物并不能使临床事件下降到较低的水平。他汀类药物升高HDL．C的幅度仅为5％-10％，对甘油三酯（TG）降低的程度为10％-20％。因此在合并HDL—C降低和（或）TG升高时，他汀类药物并不能全面改善患者的脂质谱。
Descriptive and analytic study of more than 1300 breast cancer patients in Uruguay and its relationship with prognostic factors: 230 months follow up period
Authors: G. Krygier, E. Barrios, S. Cataldi, A. Vazquez, R. Alonso, F. Estellano, E. Folle, R. Laviña, F. Delgado, C. Pressa, T. Vazquez
Journal: Journal of Clinical Oncology (2005)

857 Background: Breast cancer is the most common neoplasm arising in Uruguaian women and its incidence is very similar to those of developed countries. It accounts for 1800 new breast tumors/year and 630 deaths/year. We lack of powerfull studies dealing with survival and disease free survival of this pathology in Uruguay as well as in other latin countries, specially related to prognostic factors (tumor size, nodal involvement, histologic grade and stage at diagnosis). We analyze different covariantes among 1311 women affected with breast cancer in the same private institution in Montevideo, followed during a 230 month period (03/1985–03/2004). Methods: This study was implemented to find any relationship between well known prognostic factors (age, grade, stage, nodal involvement) and survival parameters: overall survival (OS) and disease free survival (DFS). A specific electronic data base (with more than 140 items) was elaborated for this study. For statistical analysis we used a SPSS (11.0 version) and SAS (6.0 version) programs. The statistical analysis for OS and DFS were obtained through the Kaplan Meier Method: Log rank test was implemented for univariate analysis and the Cox proportional hazard rates were applicated for multivariate analysis. Results: Ductal Infiltrating Carcinoma accounted for 81% of patients and Ductal In Situ Carcinoma represented 7.4% of cases. Stage I and II (TNM) affected 73.7% of the population. Bilateral tumors were found in 57 cases, mostly metachronic. For OS, the axillary status and the histologic grade exhibitted the highest relative ratio (RR) value: 2.49 and 2.40 respectively; the RR for the stage was 1.92 and 0.98 for the age (despite it was close to 1 it had a statistical significance, finding the worse prognostic in younger women). Data obtained for DFS concluded that the nodal status had the highest impact with a 2.2 RR followed by stage at 1.55 RR and the age at 1.35 RR Conclusions: This analysis represents the biggest one ever reported in Uruguay dealing with breast pathology and it concludes that nodal status, histologic grade and staging at diagnosis were independent prognostic factors in univariate and multivariate analysis. No significant financial relationships to disclose.
Significance of insulin-like growth factor binding protein-2 in the prognosis of breast cancer and promotion of accelerated growth and chemo-resistance in MDAMB-231 breast cancer model
Authors: A. I. So, B. Eigl, L. Fazli, D. Hunstman, N. Ivanonv, M. Pollak, S. Dunn, M. Gleave
Journal: Journal of Clinical Oncology (2005)

542 Background: Insulin like growth factor-1 (IGF1) activity is modulated by a family of IGF binding proteins (IGFBPs). The role of IGFBPs, specifically IGFBP2, in breast cancer (BCa) is poorly defined. We correlate the expression of IGFBP2 and BCa specific survival through a tissue microarray (TMA). Effect of increased IGFBP2 expression was evaluated using gain of- and loss of-function analysis in the MDA-MB231 BCa model. Methods: 348 primary human breast cancers were included in TMA construction and immunostained for IGFBP2. MB231 cells constitutively over-expressing IGFBP2 (231BP2) were generated by lentivirus transfection. IGF1R and IGFBP2 expression and response to exogenous IGF1 was compared between 231BP2 cell line and mock-transfected MB231 cell line (231M). The effect of IGFBP2 over-expression on tumor growth in vivo was determined using nude mice inoculated with either 231BP2 or 231M (n=10) +/- paclitxel (n=10). A potent antisense oligonucleotide against IGFBP2 (OGX-225, OncoGenex, Vancouver), and RNA interference (RNAi) was used to test the effects IGFBP-2 knockdown in vitro and in vivo. Results: TMA analysis show that 20 year disease-specific survival was significantly worse in those BCas highly expressing IGFBP-2 compared to low or moderate expressing tumors (63% vs. 74%, p=0.04). Spearman test demonstrates a correlation between IGFBP2 and tumor size (p=0.006) and node status (p=0.034). BP2 over-expression confers both a growth advantage in media and enhanced resistance to paclitaxel treatment. 231BP2 cells expressed higher IGF1R levels and grew faster after IGF1 treatment compared to 231M cells. In-vivo, 231BP2 tumors grew more rapidly and were more resistant to paclitaxel therapy compared to 231M control. OGX-225 and RNAi treatment inhibited tumor cell growth in vitro and in vivo through increased apoptosis. Conclusions: This study shows a significant association between tumor levels of IGFBP2 and poor survival in BCa. IGFBP2 overexpression in an ER- BCa model confers accelerated growth and chemoresistance that may be induced through increased activation of the IGF1 pathway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Oncogenex Technologies
MYC Mutation Profiling In 708 De Novo Diffuse Large B-Cell Lymphoma Demonstrates That Genetic Abnormalities In The Coding Sequence and Untranslated Regions Have Different Prognostic and Clinical Significance: A Report From The International DLBCL Rituximab-CHOP Consortium Program
Authors: Zijun Y. Xu-Monette, Alexander Tzankov, Yong Li, Carlo Visco, Santiago Montes-Moreno, Karen Dybkaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, William W. L. Choi, Joannes H.J.M. Van Krieken, Jooryung Huh, Weiyun Z. Ai, Maurilio Ponzoni, Andres J.M. Ferreri, John P. Farnen, Michael B. Moller, Jane N. Winter, Miguel A. Piris, L. Jeffrey Medeiros, Ken H. Young
Journal: Blood (2013)
A pilot study of the Vulnerable Elders Survey-13 (VES-13) as compared to Comprehensive Geriatric Assessment (CGA) to examine geriatric domains in older prostate cancer patients at risk for decline
Authors: S. G. Mohile, K. Bylow, W. M. Stadler, M. Rodin
Journal: Journal of Clinical Oncology (2006)

8539 Background: Impairments in geriatric domains (e.g. function and cognition) adversely affect health outcomes of the elderly. CGA is a key component of the treatment approach for older cancer pts, but is time-consuming. We evaluated the reliability and validity of a brief functionally-based screening tool, the VES-13, in identifying those older prostate cancer (PCa) pts at risk for impairment in the oncology clinic setting. Methods: PCa pts aged ≥ 70 yrs treated with androgen ablation followed within the oncology clinics at the University of Chicago were eligible. Pts self-completed VES-13 and CGA at baseline with VES-13 repeated 1 mth later. Physical performance and cognitive assessments were administered by a research assistant. Pts with impairment were offered follow-up in a “standard of care” frail geriatric elders program. Results: Of 36 participating pts, 50% were impaired by VES-13 (score ≥ 3). 62% of pts scored as impaired on ≥ 2 tests within the CGA exhibiting deficits in multiple geriatric domains. The reliability of the VES-13 (comparing baseline to 1 mth scores) was 0.92 (pearsons correlation coefficient). The cut-off point of 3 on the VES-13 had 72.7% sensitivity and 85.7% specificity and was highly predictive in identifying impairment (ROC AUC 0.8977) when compared to the CGA. Pts with a mean score of VES-13 ≥ 3 performed significantly worse on evaluations of Instrumental Activities of Daily Living (measures ability to live independently) (p=.006), physical performance (p=.024), comorbidity (p&lt;.001), numbers of medications (p=.022), and cognition (p=.018). In multivariate analysis, low education remained significant for VES-13 impairment after adjustment for age (p=.039). 50% of pts accepted referral to an off-site multidisciplinary geriatrics clinic. Reasons for refusal included perceived lack of need by the pt and transportation difficulties. Conclusions: Older PCa pts receiving androgen ablation have significant geriatric impairment. The VES-13 screening measure was predictive in identifying impairment when compared to the CGA and demonstrates feasibility for use in the oncology clinic setting. No significant financial relationships to disclose.