tbuckley/cabot-search huggingface dataset:
Targeting cancer with cys-diabody conjugated polymerized liposomal nanoparticles (PLNs)
Authors: Mark D. Girgis, Katelyn McCabe, Noah Federman, Anna M. Wu, Christopher Denny, Christopher Denny, James S. Tomlinson
Journal: Clinical Cancer Research (2010)

Abstract Background: Polymerized liposomal nanoparticles (PLNs) are a promising new technology for delivery of chemotherapeutic drugs to cancer cells. They are easy to prepare, biocompatible, and can carry a wide variety of therapeutics. Additionally, PLNs have the potential to be conjugated to a tumor targeting agent in hopes of delivering a cytotoxic payload directly to the cancer cells, thus minimizing systemic toxicity. Cys-diabodies are the smallest tumor antibody fragment (55 Kd) that retain the bivalency of an intact antibody. The goal of this study was to determine our ability to conjugate various engineered cys-diabody fragments to PLNs and to evaluate the ability to specifically target tumor cells based on the specificity of the diabody-tumor antigen interaction. Methods: Cys-diabody constructs against tumor antigens (ALCAM, HER2/neu, Ca19.9) were engineered, expressed in NSO myeloma cells and purified using HPLC. A cysteine residue was inserted at the C-terminus to provide the free sulhydryl group necessary for the conjugation reaction. Using malemide chemistry, cys-diabodies were conjugated to PLNs. Immunofluorescence and flow cytometry were performed to evaluate targeting of conjugated PLNs to human pancreatic and breast cancer cell lines. Unconjugated PLNs and tumor antigen negative cell lines were used as controls. Results: Anti-HER2/neu, ALCAM, and CA19.9 cys-diabodies were characterized by flow cytometry showing specific binding to MCF7 (HER2/neu positive), HPAF (ALCAM positive), and BxPC3 (CA19.9 positive) cell lines, respectively. No binding was observed to antigen-negative cell lines nor with the unconjugated PLNs. Conjugation of cys-diabodies to PLNs was indicated by immunofluorescence showing specific binding of PLN-cys-diabody conjugates to breast and pancreatic cancer cells in vitro (Figure 1). These data were also confirmed by flow cytometry. Conclusions: We have demonstrated the ability to conjugate our PLN with engineered anti-tumor cys-diabodies. Furthermore, we have demonstrated that after conjugation, the PLNs demonstrate specific tumor-cell targeting based on the specificity of the diabody-tumor antigen affinity. These studies represent an important first step in the development of targeted PLNs with the ultimate goal of delivering high doses of a chemotherapeutic directly to the cancer cells.
Total serum IgE is associated with asthma independently of specific IgE levels. The Spanish Group of the European Study of Asthma
Authors: J Sunyer, JM Anto, J Castellsague, JB Soriano, J Roca
Journal: European Respiratory Journal (1996)

In this study we aimed to assess whether the association between asthma (defined by symptoms and bronchial responsiveness) and total immunoglobulin E (IgE) levels was independent of specific IgE levels to common aeroallergens. A general population-based sample, supplemented with symptomatic individuals, comprising 1,916 young adults, aged 20-44 years, from five areas of Spain, performed a face-to-face respiratory questionnaire, and spirometry, and had total and specific serum IgE levels to mites, pets and moulds recorded. In 1,626 of the subjects, a dose-response methacholine challenge test was completed. Subjects reporting current attacks of asthma showed an association with total IgE (odds ratio (OR) for IgE &gt; 100 kU.L-1 = 4.73, 95% confidence intervals (95% CI) = 2.01-11.12, adjusted for specific IgE, sex, age, smoking, forced expiratory volume in one second (FEV1), and area), which did not vary by bronchial responsiveness. The association between total IgE and asthma also occurred among those with negative specific IgE antibodies (OR 18.0; 95% CI 13.9-120). Individuals with current wheezing and bronchial responsiveness without attacks of asthma also showed an adjusted association with total IgE (OR 4.96; 95% CI 2.32-10.6), which remained for persons without specific IgE (OR 5.86; 95% CI 2.18-1.7). These findings reinforce previous evidence that asthma is associated with increased levels of total IgE, even in subjects negative for specific IgE to common aeroallergens.
A trial of ranitidine in asthmatic children and adolescents with or without pathological gastro-oesophageal reflux
Authors: PM Gustafsson, NI Kjellman, L Tibbling
Journal: European Respiratory Journal (1992)

In order to study the importance of gastro-oesophageal reflux (GOR) as a trigger of asthma the effect of inhibition of gastric acid secretion on asthma was assessed in a double-blind, cross-over, placebo-controlled trial over four weeks in 37 children and adolescents (mean age 14 yrs) with bronchial asthma. Ranitidine 300 mg, (150 mg if B.W. was less than 40 kg) was given as a single evening dose during four weeks. In previous investigations 18 of the 37 patients had been shown to have pathological GOR by 24 h pH monitoring in the oesophagus. The remaining 19 patients with normal GOR served as controls for possible effects of ranitidine on asthma, not related to reduction of GOR. A modest (30%) but statistically significant reduction of nocturnal asthma symptoms was produced by ranitidine in the patients with pathological GOR when compared to those with normal GOR. There was a significant correlation between the improvement in asthma symptoms and the degree of acid reflux. Side-effects of ranitidine were negligible. Acid reflux appears to be only a weak stimulus for bronchoconstriction in children and adolescents with bronchial asthma and pathological GOR. Further confirmative trials with more potent inhibitors of gastric acid secretion are, however, warranted.
Eugenol dose-dependent improvement of pulmonary lesions in lipopolysaccharide acute lung injury
Authors: Clarissa Magalhães, Natália Casquilho, Mariana Machado, Douglas Riva, Rodrigo Fortunato, José-Henrique Leal Cardoso, Leonardo Travassos, Walter Zin
Journal: European Respiratory Journal (2011)

Background:  Eugenol, a methoxyphenol component of clover oil, inhibits NF-κB activation induced by TNF-α in LPS-stimulated macrophages.   Aim:  The aim of the study was to evaluate the effects of different doses of eugenol on lung mechanics, histology and cytokines in LPS-injured lungs.   Methods:  59 female BALB/c mice were randomly divided in 9 groups (n=5-8/group). Mice received intratracheally sterile saline solution (0.05 ml) or LPS (10 μg in 0.05 ml of saline); 6 h later they received sterile saline (0.2 ml) and Tween 1% (C, and L groups) or different doses of eugenol: 16, 65, 114, 160, 650 or 1140 mg/kg in saline (0.2 ml) and Tween 1% (LE1, LE2, LE3, LE4, LE5, LE6 and LE7 groups, respectively) by gavage. Mice were evaluated 24 h after receiving LPS. In another 18 mice [C=6, L=6, E=3 (saline followed by eugenol) and LE=3]; in these animals TNF-α and IL-1β were detected by ELISA in lung homogenates at 6 (C=3 and L=3) and 24 h (C=3, L=3, E=3 and LE=3) after LPS administration. One-way ANOVA followed by Tukey test was used (α=5%).   Results:  Static elastance, viscoelastic component of elastance and viscoelastic resistive pressure were higher in L group (33.05, 5.01 cmH 2 O/ml, and 1.00 cmH 2 O, respectively) than in C (22.13, 3.62 cmH 2 O/ml, and 0.71 cmH 2 O), accompanied by alveolar collapse and collagen fiber deposition; eugenol reduced the parameters in LE4 group (except alveolar collapse) and abolished them from LE5 (23.34, 3.62 cmH 2 O/ml, and 0.72 cmH 2 O) onwards. LE group showed smaller TNF-α and IL-1β levels than L mice. LE behaved similarly to C and E groups.   Conclusion:  Eugenol exhibits an  in vivo  anti-inflammatory dose-dependent action in LPS-induced lung injury.  Supported by: CNPq, FAPERJ, MCT.
Clinical significance of bone marrow metastases as detected using the polymerase chain reaction in patients with breast cancer undergoing high-dose chemotherapy and autologous bone marrow transplantation.
Authors: K K Fields, G J Elfenbein, W L Trudeau, J B Perkins, W E Janssen, L C Moscinski
Journal: Journal of Clinical Oncology (1996)

PURPOSE The present study evaluates the clinical significance of detection of cytokeratin 19 (K19) in the bone marrow of patients with breast cancer undergoing high-dose chemotherapy (HDCT) and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS We studied retrospectively cryopreserved bone marrow aspirates from 83 patients with high-risk stage II, III, and IV breast cancer obtained before bone marrow harvest but after induction chemotherapy. All samples were histologically negative for metastases. Polymerase chain reaction (PCR) for K19 was performed according to methods described previously and results were correlated with the probability of relapse following HDCT and ABMT. RESULTS The incidence of occult metastases as defined by PCR for K19 message was 52% for 19 stage II, 57% for 14 stage III, and 82% for 50 stage IV patients (two-tailed P = .0075, chi 2 test). The probability of relapse at 3 years after ABMT was 32% and 94% for K19-positive stage II/III and stage IV patients, respectively, versus 10% and 14% for K19-negative stage II/III and stage IV patients, respectively. The difference was significant for stage IV patients (two-tailed P = .0002). CONCLUSION It has been shown that PCR is a highly sensitive method to detect K19 message in the bone marrow. The incidence of K19 positivity in bone marrow increases significantly with advancing stage. In patients with breast cancer, especially metastatic breast cancer, undergoing HDCT and ABMT, the presence of K19 is associated with a poor prognosis.
Survival after relapse of low-grade non-Hodgkin's lymphoma: implications for marrow transplantation.
Authors: D J Weisdorf, J W Andersen, J H Glick, M M Oken
Journal: Journal of Clinical Oncology (1992)

PURPOSE Despite modern therapy, patients with low-grade non-Hodgkin's lymphomas (NHLs) have a median survival of only 7 to 10 years. To determine factors that predict for short survival after relapse and thus to identify candidates for intensive investigational studies including bone marrow transplantation, we have analyzed the combined results of three Eastern Cooperative Oncology Group (ECOG) trials of initial chemotherapy for lymphoma. PATIENTS AND METHODS All 466 patients who achieved initial complete response (CR) or partial response (PR) and had a subsequent relapse were evaluated (median follow-up, 12.6 years). Multivariate regression analysis within a training set (two thirds of cases) was verified in the remaining one-third (validation set) of cases. RESULTS Age younger than 60 years, CR, and response duration were significantly associated with longer survival after relapse. Multivariate analysis developed a predictive model that identified shorter survival in patients greater than or equal to 60 years, regardless of CR or response duration. Patients younger than 60 years with an initial CR of more than 1 year had a median survival of 5.9 years, those with a PR of more than 1 year had a median survival of 4.2 years, and those with a CR or PR of less than or equal to 1 year, 2.4 years (P less than .0001). Even the most favorable group had a 10-fold greater mortality compared with age-adjusted United States population rates. CONCLUSIONS These data suggest that patients with low-grade NHLs with a less than or equal to 1-year response period have poor survival after relapse and may be candidates for aggressive salvage therapy, including transplantation. Longer initial responses lead to better survival after relapse. Clinical trials seeking to demonstrate an advantage for new treatments including transplantation will require long follow-up and comparison to control populations for meaningful analysis.
Abstract 9298: Detection of Atrial Fibrillation Using an iPhone 4S
Authors: Oscar Maitas, Jinseok Lee, Dionyssios Robotis, Peter Bourell, Ki H Chon, David D McManus
Journal: Circulation (2012)

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with increased risk for stroke, heart failure, and death. Timely detection of AF can be challenging using traditional diagnostic tools. Smartphone use is increasing among individuals susceptible to AF and may provide an inexpensive and user-friendly means to diagnose AF. Our aim was to to develop methods for accurately detecting AF using a smartphone camera. METHODS: In this prospective clinical investigation, we recruited 52 adults presenting to the University of Massachusetts Medical Center for electrical cardioversion of AF. Participants underwent rhythm assessment using a novel iPhone 4S application before and after electrical cardioversion. Two minutes of pulsatile time series recordings were obtained from each participant’s index finger (placed on the iPhone 4S camera). The iPhone 4S application used 2 statistical methods (Root Mean Square of Successive RR Differences; Shannon Entropy) to examine heart beat intervals and beat-to-beat variability. We used receiver operating characteristic (ROC) curves to establish a threshold for sensitivity, specificity, and predictive accuracy of our application as compared to the gold-standard of 12-lead electrocardiogram. RESULTS: The AF detection accuracy was 99.14% (sensitivity of 99.77% and specificity of 98.58%) for each sample when a combination of the three signal processing techniques were applied compared to the gold-standard electrocardiographic recordings. All of the 52 AF episodes were detected. In addition, we tested on 29 healthy subjects and found that the accuracy (specificity) was 99.51%. CONCLUSIONS: Our iPhone 4S AF Detection application performed well, demonstrating excellent sensitivity, specificity, and accuracy for beat-to-beat discrimination of AF from normal sinus rhythm. For clinical applications, the relevant objective is to detect the presence of AF from a given recording. Using this criterion, the AF detection accuracy was 100% based on a 2-minute sample. Our findings show that AF can be accurately detected from pulsatile signals in the human fingertip using the camera of an iPhone 4S.
Upper urinary tract cancer: Prognostic factors for bladder tumours development and systemic relapse
Authors: F. Merlin, M. Riolfi, T. Sava, F. Consoli, C. Griso, P. Manno, A. B. Porcaro, C. Ghimenton, L. Comunale, G. Cetto
Journal: Journal of Clinical Oncology (2006)

14560 Background: Transitional cell carcinomas (TCC) of the renal pelvis and ureter are relatively uncommon. An important characteristic of TCC is multifocality throughout the all urinary tract simultaneously and/or subsequently. To clarify the association between UTTCC and bladder tumors, we retrospectively analysed 86 patients with UTTCC in order to evaluate prognostic factors for recurrence and to identify risk factors for development of bladder cancers. Methods: All 86 upper tract transitional cell carcinoma patients (pts) were treated surgically between January 1988 and July 2005. Median age was 69 years (range: 34–91). We observed a male predominance (71%) and 78% of patients were heavy smokers. Forty-five (52.3%) patients had a diagnosis of bladder transitional carcinoma. The median age of this group of patients was 70 range 40–87). In fifteen cases (17%), bladder tumour occurred first than upper tract neoplasia; in 14 patients bladder and upper tract tumours were synchronous. Results: Median survival was 97 months; 49 (57%) patients are alive and 43 are disease-free. Grading, stage T, lympho-vascular invasion and squamous differentiation were significant prognostic factors for systemic relapse (p &lt; 0.05). Twenty-eight pts (32.5%) developed subsequent transitional bladder cancer after a median time of 12 months; multifocality of primitive tumours was significant predictive factor. Invasive UTTCC were less likely associated with bladder cancer. We observed that superficial bladder cancer developed more frequently in pts with well differentiated (G1–2) primitive cancer (90% of cases), without lympho-vascular invasion and with history of heavy smoke exposition. Conclusions: In our study, T, N and G confirmed to be the most important prognostic factors for systemic relapse. Lympho-vascular invasion highly predicts metastasis. Our analysis highlights that upper urinary tract cancers seem to have different history and different pattern of association with bladder tumours, according to specific prognostic factors. The development of recurrent superficial bladder cancer is more frequently associated with small well differentiated multifocal upper tract tumours.Therefore follow-up should be oriented according to these characteristics. No significant financial relationships to disclose.
Combined chemotherapy and radiotherapy for patients with breast cancer and extensive nodal involvement.
Authors: O Ung, A O Langlands, B Barraclough, J Boyages
Journal: Journal of Clinical Oncology (1995)

PURPOSE This retrospective review examines local control, freedom from distant failure, and survival for patients with nonmetastatic breast cancer with extensive nodal disease (&gt; 10 nodes, 45 patients; or &gt; or = 70% involved nodes, if &lt; 10 nodes found, 19 patients). All patients received chemotherapy and radiotherapy following mastectomy. PATIENTS AND METHODS Sixty-four patients were treated between January 1980 and December 1988 at Westmead Hospital, Westmead, NSW Australia. The median follow-up duration for surviving patients was 91.5 months (range, 56 to 121). The median age was 51 years, and the median number of positive nodes was 11. Four successive protocols evolved, each with three phases, as follows: induction chemotherapy (doxorubicin or mitoxantrone, plus cyclophosphamide; three cycles), radiotherapy (50 Gy in 25 fractions to chest wall and regional nodes), then chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF]) of progressively shorter duration. Radiotherapy and chemotherapy were concurrent in the fourth regimen. RESULTS One patient (1.5%) developed local recurrence before distant relapse, and seven patients (11%) developed local and/or regional recurrence simultaneously or after distant relapse. The 5-year actuarial freedom from distant relapse and overall survival rates were 45% and 65%, respectively. Overall survival did not vary significantly by menopausal status, nodal subgroup, or dose-intensity. There were no treatment-related deaths. CONCLUSION Combined chemotherapy and radiotherapy in standard dosage is an acceptable approach following mastectomy for patients with extensive nodal involvement at high risk for local recurrence and distant relapse. This approach should be considered standard best therapy for any randomized trials that examine high-dose chemotherapy or bone marrow transplantation for this subgroup of patients.
Depression in Patients With Lung Cancer: Prevalence and Risk Factors Derived From Quality-of-Life Data
Authors: Penelope Hopwood, Richard J. Stephens
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To evaluate self-reported depression rates in patients with inoperable lung cancer and to explore demographic, clinical, and quality-of-life (QOL) factors associated with depression and thus identify patients at risk. PATIENTS AND METHODS: Nine hundred eighty-seven patients from three palliative treatment trials conducted by the Medical Research Council Lung Cancer Working Party formed the study sample. 526 patients (53%) had poor prognosis small-cell lung cancer (SCLC) and 461 patients (47%) had good prognosis non–small-cell lung cancer (NSCLC). Hospital Anxiety and Depression Scale data and QOL items from the Rotterdam Symptom Checklist were analyzed, together with relevant demographic and clinical factors. RESULTS: Depression was self-rated in 322 patients (33%) before treatment and persisted in more than 50% of patients. SCLC patients had a three-fold greater prevalence of case depression than those with NSCLC (25% v 9%; P &lt; .0001). An increased rate for women was found for good performance status (PS) patients (PS of 0 or 1) but the sex difference reduced for poor PS patients (PS of 3 or 4) because of increased depression rates for men (χ 2 for trend, P &lt; .0001). Multivariate analysis showed that functional impairment was the most important risk factor; depression increased by 41% for each increment on the impairment scale. Pretreatment physical symptom burden, fatigue, and clinician-rated PS were also independent predictors, but cell type was not. CONCLUSION: Depression is common and persistent in lung cancer patients, especially those with more severe symptoms or functional limitations. Psychologic screening and appropriate intervention is an essential part of palliative care.
Resistance to Small Amounts of Bittner Mammary Tumor Virus in Offspring of C57BL Female Mice With the Virus
Authors: P. Bentvelzen
Journal: JNCI Journal of the National Cancer Institute (1968)

After implantation of a diethylstilbestrol pellet in female hybrids of the C57BL and BALB/c mouse strains without Bittner mammary-tumor virus, the incidence of mammary tumors was only ± 8% at 24 months of age. Introduction of the Bittner virus into these hybrids by means of foster nursing on BALB/cfC3H females augmented the tumor incidence to about 60% at an average age of 14 months. C57BL females carrying the Bittner virus did not transmit enough virus to their (C57BL × BALB/c)F1 offspring to produce mammary tumors. When these hybrids were foster-nursed only on the first day of life by BALB/cfC3H, about 30% developed mammary tumors. Only 10% of the offspring of C57BL females carrying the virus, foster-nursed for 1 day on BALB/cfC3H females, had mammary tumors. Since ordinary C57BL females do not transfer resistance to the Bittner virus to their offspring, it was concluded that those with the virus transfer antibodies to their progeny; these antibodies can neutralize small amounts of the Bittner virus. BALB/cfC3H mice carrying the Bittner virus cannot transfer such a resistance to their offspring. When (♀ BALB/c × ♂ C57BL)F1 mice were foster-nursed only on the third day of life by BALB/cfC3H females, 59% developed mammary tumors. This indicated that foster nursing the first day of life provided a threshold dose of Bittner virus. No C57BL and BALB/c hybrids foster-nursed only on the first day of life by C57BL females with the Bittner virus developed mammary tumors. This indicated that the Bittner virus is poorly transmitted by C57BL females. How the immunological reaction of the C57BL strain against the virus, together with other genetically controlled systems, causes resistance to the development of mammary tumors is discussed.