tbuckley/cabot-search huggingface dataset:
Abstract B45: A search for ideal siRNA targets involved in pathway cross-talks for combinational silencing in human cancer cells
Authors: Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Hasan Uludag
Journal: Clinical Cancer Research (2015)

Abstract The heterogeneity in the pathways involved in enhanced cell proliferation and survival mechanisms, as well as the mechanisms playing a major role in development of drug resistance, is an important obstacle in cancer treatment. Signaling axes such as PI3K-AKT, Ras-Raf, MEK-ERK, and JAK-STAT pathways have not only been established as major processes involved in enhanced proliferation and activation of the transcription of multiple anti-apoptosis proteins, but are also shown to be interconnected in forming a vast intracellular signaling network. RNA interference, and more specifically, small interfering RNA (siRNA), is a post-transcriptional down-regulation of the expression of a specific protein, and has been studied extensively in the last decade as not only an investigational tool, but also as a therapeutic approach especially in cancer treatment. In the present study, we undertook a systematic approach to simultaneous silencing of two proteins involved in intracellular signaling network in order to inhibit more than one pathway involved in proliferation and survival of cancer cells. After carefully selecting the proteins with pivotal roles in cell survival through diverse pathways, we studied silencing each protein individually and in all possible dual combinations, and evaluated the cell response as the mRNA level of the selected proteins as well as the viable cell number. Our studies reveled that silencing JAK2, STAT3, and JUN have a significant effect on the expression level of anti-apoptotic proteins, e.g., Mcl-1 and survivin, and could negatively impact the survival of MDA435 cells. These results indicate a promising potential for combinational siRNA silencing as an effective anticancer strategy. Citation Format: Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Hasan Uludag. A search for ideal siRNA targets involved in pathway cross-talks for combinational silencing in human cancer cells. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B45.
Pathological changes in the skeletal muscles in COPD patients
Authors: Mohamed Elnady, Maysa Sharaf El-Din, Yosef Amin, Ali El-Hindawy
Journal: European Respiratory Journal (2011)

Background:  Peripheral muscle weakness is a major problem in COPD, contributing to exercise intolerance and decreased health status. The loss of muscle mass has been described in those patients, but, little data are reported regarding the morphology of limb muscles.   Objectives:  To study the pathological changes that occurs in the peripheral skeletal muscles in COPD Patients.   Methods:  50 COPD patients were chosen from the outpatient clinic of chest diseases, Cairo University Hospitals. Muscle biopsies were taken from the left Vastus lateralis under local anesthesia by Abram9s needle and subjected to histopathological examination after staining with Hematoxlin and Eosin. The biopsies were compared to specimens taken from 10 healthy control subjects of the same sex and age group.   Results:  Strong correlation was found between the severity of COPD and the degree of muscle atrophy graded from zero (normal) to 4 (marked atrophy) according to number of foci of atrophy. The one patient in stage I & 69% of patients in stage II COPD were found to have normal biopsy. Stage III; showed both mild atrophy in (45.5%) & moderate atrophy in (41%) of patients. Stage IV showed moderate atrophy in (64.3%). Marked degree of atrophy were belonged to stage III; 9% and IV; 7.2% of patients. A statistically significant positive correlation was found between degree of muscle atrophy and (age, smoking index & number of exacerbations/year).   Conclusion:  COPD patients showed variable degrees of peripheral skeletal muscle atrophy correlated to disease severity. Progression of COPD is associated with progression of the muscle affection.
Influence of body mass index on asthma severity and control: A cross-sectional study
Authors: Shinobu Osanai, Toshiyuki Ogasa
Journal: European Respiratory Journal (2013)

Background: Elevations in body mass index (BMI) are reported to affect asthma condition and response to treatment. OBJECTIVES: We investigated relationship between BMI and the asthma severity and control. METHODS: Subjects were 191 asthmatic patients treated at Asahikawa Medical University Hospital. Their backgrounds, asthma symptom and short-acting beta(2)-agonist use were surveyed from the medical charts. They were assessed according to GINA classification. Their latest vital capacity (VC), forced expiratory volume in one second (FEV1) and inspiratory capacity (IC) as a base pulmonary function, and fast blood glucose (FBS) and serum total cholesterol (TC) measured within six months of the study as metabolic factors were studied. We divided the subjects to three groups (GINA Step 1 + 2, Step 3 and Step 4) and analysed relationship between GINA Step and other factors. RESULTS: In the male subjects, the means of BMI (SD) in Step 1 + 2, Step 3, Step 4 were 22.2 (2.6), 23.4 (3.7), 26.0 (5.8), respectively. In the female subjects, the means of BMI (SD) in Step 1 + 2, Step 3, Step 4 were 22.0 (4.0), 22.4 (4.6), 25.0 (4.6), respectively. There were no significant differences in the metabolic factors among three groups of the both sexes. In the male subjects, %FEV1 in Step 3 and Step 4 were lower than that in Step 1 + 2. Also, %IC / VC were higher than that in Step 1 + 2. In the female subjects, those association was not observed. A multivariate regression analysis was performed to Steps and BMI, lung function and metabolic factors. We found positive associations between GINA Step and BMI. CONCLUSION: This study suggests a significant association between BMI and the asthma severity and control.
Plasma Cell Neoplasm Arising In a CAF&lt;sub&gt;1&lt;/sub&gt; Mouse. Characteristics and Response to Certain Chemotherapeutic Agents
Authors: Sidney T. Yancey
Journal: JNCI Journal of the National Cancer Institute (1964)

A plasma cell tumor (YPC-1) that arose spontaneously in the ileocecal region of a (BALB/c × A/Ln)F1 (CAF1) mouse is described. Microscopic examination of the ileocecal mass revealed a second tumor, an adenocarcinoma of the cecum in close association with the plasma cell tumor. YPC-1 has been carned through 64 intraperitoneal transplant generations. It grows in all inoculated CAF1 mice and has never been observed to regress spontaneously. An increased amount of γ-globulins can be demonstrated in the serum of mice bearing subcutaneous implants of YPC-1; Bence Jones protein has not been demonstrated in the urine. The regularity of the growth pattern of this tumor makes it useful for bioassay of antitumor drugs. The sensitivity of YPC-1 to early and late treatment with several agents has been evaluated. Median survival times of mice bearing either intraperitoneal or subcutaneous implants of YPC-1 were increased twofold or more by cyclophosphamide and mechlorethamine. Relatively slight effects (8–33% increases in median survival) were obtained with 6-mercaptopurine, methotrexate, prednisolone, and X radiation. The sensitivity of YPC-1 to mechlorethamine is unusual and suggests that YPC-1 might be a good bioassay system for the study of comparative response to mechlorethamine derivatives and alkylating agents in general.
Quantitative real-time PCR tests for diagnostic and prognostic purposes in cases of legionellosis
Authors: M. Maurin, L. Hammer, B. Gestin, J.F. Timsit, O. Rogeaux, F. Delavena, J. Tous, O. Epaulard, J.P. Brion, J. Croizé
Journal: Clinical Microbiology and Infection (2009)
Anxiety and congenital central hypoventilation syndrome
Authors: D S Pine, D E Weese-Mayer, J M Silvestri, M Davies, A H Whitaker, D F Klein
Journal: American Journal of Psychiatry (1994)

It has been hypothesized that individuals who cannot perceive elevations of CO2 will be less anxious than individuals with intact CO2 perception. To test this hypothesis, children with congenital central hypoventilation syndrome, who have a potentially lethal chronic illness associated with lack of CO2 perception and thus provide a natural experimental group, were studied.Rates of anxiety symptoms and disorders in children with congenital central hypoventilation syndrome (N = 13) were compared with rates in an age-matched, nonreferred group of community subjects (N = 292) that included subgroups of children with asthma (N = 15) and other chronic medical illnesses (N = 66). Anxiety symptoms were assessed with information obtained from structured interviews of the parents, which provided both total symptom scores and DSM-III-R diagnoses.The children with congenital central hypoventilation syndrome exhibited significantly fewer anxiety symptoms than all other comparison subjects. Two of these children (15%) met criteria for anxiety disorders, a rate lower than that of the whole community group (24%) and of the chronically ill comparison subgroups (32%-47%). The largest difference in the prevalence of disorder emerged between the children with congenital central hypoventilation syndrome (15%) and those with asthma (47%). In the comparison of children with congenital central hypoventilation syndrome and children with other chronic illnesses, a priori analysis showed that the former had significantly lower rates of disorders that have been linked to panic in the literature.This study supports theories of anxiety that implicate CO2 perception in the pathophysiology of panic and related anxiety states.
Bench test of a mass spectrometer based multiple-breath washout system using a realistic lung model
Authors: Florian Singer, Birgitta Houltz, Paul Robinson, Philipp Latzin, Per Gustafsson
Journal: European Respiratory Journal (2012)

Background Lung volume measurement accuracy of multiple-breath washout (MBW) systems should be validated under realistic conditions. Here we used a previously described lung model (ERS meeting 2011) incorporating BTPS conditions to validate a customized mass spectrometer (AMIS 2000; Innovision) MBW setup used in a series of clinical studies.

Methods Functional residual capacity (FRC) measurement accuracy was assessed across a range of FRCs (430-4120 mL), tidal volumes (210-1010 mL), and respiratory rates (36-12 min-1). A wash-in inert gas mixture containing 4% sulfur hexafluoride (SF6) and 4% helium (He) was used for MBW. 63 MBWs were conducted over two test days. Measured gas and flow signals were processed in custom software (TestPoint). FRC was calculated as cumulative expired inert gas volume divided by the difference of MBW start minus end inert gas concentration.

Results Mean (range) coefficient of variation of FRC was 0.6 (0.1-2.2)%. Mean difference between measured and nominal FRC was 46.7 mL (1.7%), upper and lower limits of agreement were 155.3 mL (5.1%) and -62.0 mL (-1.8%), respectively. Of 126 FRCs, 124 (98%) were within 5% of the nominal FRC, mean error (range) was 2.1 (0.1-6.0)%. Error was associated with respiratory rate (R2 = 0.23). FRC was reproducible between tests, coefficient of repeatability was 73 mL (3.4%) and similar using either He or SF6 for FRC calculation.

Conclusion Using a lung model previously shown to be suitable for MBW system validation under physiological conditions, the custom mass spectrometer MBW system precisely and reproducibly measures FRCs ranging from preschool to adult lung volumes.
Clinical evaluation of circulating serum sialyl Tn antigen levels in patients with epithelial ovarian cancer.
Authors: H Kobayashi, T Terao, Y Kawashima
Journal: Journal of Clinical Oncology (1991)

Sialyl Tn antigen (NeuAc alpha 2----6GalNac alpha 1----0-Ser/Thr [STN]) with antigenic specificity in the core structure of mucin-type carbohydrate chains has been determined. In the present study, we evaluated the clinical significance of this new carbohydrate antigen, STN, in patients with epithelial ovarian cancer. With the use of a radioimmunoassay developed to detect STN antigen in serum, elevated (greater than or equal to 32.6 U/mL) antigen levels were observed in 50.0% of patients with ovarian cancer. In contrast, 3.8% of healthy individuals had STN antigen levels greater than or equal to 32.6 U/mL. In 9.6% of patients with benign gynecologic diseases and 0% of pregnant women, there were elevated levels of STN antigen. There was a significant difference (P less than .001) in STN antigen levels between patients with ovarian cancer and patients with benign gynecologic diseases, pregnant women, or the controls. The mean +/- SD for all evaluated samples of ovarian cancer was 109.2 +/- 146.8 U/mL. Both the mean values and the positive rate increased as the stage advanced. Classified according to the histologic type, the highest positive rate (61.0%) was observed in mucinous adenocarcinoma. The usefulness of STN antigen as a circulating tumor marker in ovarian cancer was estimated as follows: sensitivity 50.0%, specificity 93.5%, positive predictive value 72.2%, negative predictive value 84.7%, and diagnostic value 46.8%. Serum STN antigen levels were elevated in 12 of 33 patients with ovarian cancer who had serum CA 125 antigen levels less than 35 U/mL. While CA 125 antigen levels were elevated in 74.6% and STN antigen levels were elevated in 50.0% of the same population, the use of both assays indicated the sensitivity of detection of 83.8% in the population studied.
XAGE-1b and p53: Potential targets for immunotherapy of non-small cell lung cancer (NSCLC)
Authors: Mehrdad Talebian Yazdi, Nikki M. Loof, Jouke T. Annema, Cornelis J. Melief, Pieter S. Hiemstra, Marij J.P. Welters, Jaap Oostendorp, Sjoerd H. van der Burg
Journal: European Respiratory Journal (2012)

Induction of immune responses specifically against tumor-associated antigens by vaccination is a promising approach for cancer immunotherapy. XAGE-1b is a cancer-testis antigen that is aberrantly expressed in lung adenocarcinoma. p53 is a tumor suppressor protein that is over-expressed in NSCLC. We investigated local (primary tumor, tumor draining lymph node (TDLN)) and systemic (peripheral blood) immune responses against XAGE-1b and p53 in lung adenocarcinoma.  Tissue and blood samples from 6 lung adenocarcinoma patients were obtained. Tumor-infiltrating lymphocytes (TIL) were isolated from tumor tissue by culturing for 3 weeks. Lymph node mononuclear cells (LNMC) were obtained from TDLN and cultured in 3 ways: medium alone (LN neg), stimulated once by XAGE-1b (LN XAGE) or p53 overlapping peptides (LN p53). Peripheral blood mononuclear cells (PBMC), TIL and the 3 LNMC cultures were analyzed for antigen-specificity by a 4-day proliferation assay and in supernatants taken at day 2 cytokine release was determined.  In 1 out of 6 patients, XAGE-1b induced proliferation in LN XAGE and IFNγ release in LN XAGE and TIL. In another patient, XAGE-1b induced proliferation in PBMC and LN neg, but no IFN-γ release. In 3 out of 6 patients, a p53-induced proliferation was observed in LN p53, which was accompanied by IFN-γ release in 2 patients. In one patient, p53 induced TNF-α release in TIL.  These preliminary data show T-cell immunity to XAGE-1b and p53 in lung adenocarcinoma indicating that these antigens are potential targets for immunotherapy. More patients are needed to define strength, breadth and phenotype of this antigen-specific response and its relation with antigen expression in the primary tumor.
Specific Therapy in Severe Fetal Intrauterine Growth Retardation: Failure of Prostacyclin
Authors: S A Steel, J M Pearce
Journal: Journal of the Royal Society of Medicine (1988)

Two case histories of severe, early onset intrauterine growth retardation are presented. Intravenous prostacyclin was administered in an attempt to promote fetal growth and thus prolong the pregnancy, but was unsuccessful and resulted in intrauterine death in each case. The possible reasons for the failure of this treatment and alternative therapeutic options are discussed.
The Epworth sleepiness scale 23 years after: Is daytime sleepiness still a valid screening tool for sleep apnea
Authors: Hrvoje Puretic, Davor Plavec, Gordana Pavlisa, Ervin Zuljevic, Miroslav Samarzija, Marko Jakopovic
Journal: European Respiratory Journal (2014)

OBJECTIVE  Sleep apnea (SA) is a common medical problem burdened by numerous comorbidities and economical costs. Since the introduction of the Epworth Sleepiness Scale (ESS) as a screening tool, daytime sleepiness was considered the most common and prominent symptom of SA. Aim of this study was to reevaluate diagnostic validity of ESS compared to the results of polysomnography (PSG) being a gold standard for SA diagnosis.  METHODS  Total of 266 patients (mean age 57.9±11.6 yrs; 189 men and 77 women), referred to our sleep lab because of probable SA, were given ESS followed by an overnight PSG study. The ESS values were compared to PSG apnea hypopnea index (AHI) with sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA) calculated for ESS. The positive cut-off value for ESS was ≥10 and for AHI ≥5.  RESULTS  Ninety two subjects (34.6%) had positive ESS. SA was diagnosed by PSG in 213 (80.1%) subjects: 46 (17.3%) having mild, 37 (13.9%) moderate and 130 (48.9%) severe apnea. Most subjects with positive ESS (88.0%) were found to have positive PSG, but unexpectedly, most subjects with negative ESS (75.9%) were also PSG positive (42% of them with AHI ≥30). Area under ROC curve for ESS was 0.59 (95% CI, 0.52-0.68) with SE of ESS being 38.0%, SP 79.3%, PPV 88.0%, NPV 24.1% and DA 46.2%.  CONCLUSION  We found that daytime sleepiness measured by ESS is not a valuable screening tool for detecting SA patients, especially when the test is negative. Other screening tests that do not rely solely on daytime sleepiness but on other parameters should be considered (e.g. Berlin questionnaire, Stop bang).
Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside.
Authors: P O Livingston, G Y Wong, S Adluri, Y Tao, M Padavan, R Parente, C Hanlon, M J Calves, F Helling, G Ritter
Journal: Journal of Clinical Oncology (1994)

PURPOSE To perform a double-blind randomized trial with American Joint Commission on Cancer (AJCC) stage III melanoma patients for the following reasons: (1) to confirm our previous finding that patients with antibodies against the melanoma differentiation antigen GM2 have an improved prognosis, and (2) to demonstrate clinical benefit from GM2 antibody induction. PATIENTS AND METHODS One hundred twenty-two patients with AJCC stage III melanoma who were free of disease after surgery were randomized: 58 to receive treatment with the GM2/BCG vaccine, and 64 to receive treatment with bacille Calmette-Guèrin (BCG) alone. All patients were pretreated with low-dose cyclophosphamide (Cy). RESULTS GM2 antibody was detected in 50 of 58 patients treated with GM2/BCG and seven of 64 patients treated with BCG alone. With a minimum follow-up period of 51 months, there was a highly significant increase in the disease-free interval (P = .004) and a 17% increase in overall survival (P = .02) in these 57 antibody-positive patients, confirming our earlier experience. Exclusion of all patients with preexisting GM2 antibodies (one in the GM2/BCG group and five in the BCG group) from statistical analysis resulted in a 23% increase in disease-free interval (P = .02) and a 14% increase in overall survival (P = .15) at 51 months for patients treated with the GM2/BCG vaccine. However, when all patients in the two treatment groups were compared as randomized, these increases were 18% for disease-free interval and 11% for survival in the GM2/BCG treatment group, with neither result showing statistical significance. CONCLUSION (1) Vaccination with GM2/BCG induced immunoglobulin M (IgM) antibodies in most patients. (2) GM2 antibody production was associated with a prolonged disease-free interval and survival. (3) Comparison of the two arms of this trial as randomized fails to show a statistically significant improvement in disease-free interval or survival for patients treated with GM2/BCG vaccines.
FREQUENCY OF SEIZURES IN EPILEPSY
Authors: HARRY A. PASKIND, MEYER BROWN
Journal: American Journal of Psychiatry (1939)

The frequency of seizures has heretofore been reported mainly in institutional deteriorated patients. A study of the frequency of seizures in a group of 317 non-institutional, non-deteriorated patient with epilepsy discloses that seizures are significantly less frequent in such a group than they are in deteriorated institutional patients.
Copeptin application in severe community-acquired pneumonia (SCAP) severity assessment and outcomes
Authors: Oksana Omelyanenko, Alexander Makarevich, Paulina Jagus, Joanna Chorostowska-Wynimko, Tatyana Rybina, Elena Amelchenko
Journal: European Respiratory Journal (2012)

Background: Appropriate early prognostic assessement is crucial for SCAP patients management.   Aim: We aimed to investigate copeptin levels in SCAP patients and their relationship with in-hospital outcomes (in-hospital mortality (IHM), length of in-hospital stay(LOS), duration of ICU stay), disease specific complications, need for invasive mechanical ventilation (IMV) and vasopressor support (VS).   Methods: 20 ICU patients with proven SCAP CURB-65 class 3, 4 were enrolled to the study. Serum CP values were measured within the first 24 hours after the hospitalization.   Results: Increasing CAP severity was associated with increased CP values(r=0,53;p=0,02). CP levels on admission appeared to be higher in CURB-65 4th class patients vs the 3rd class patients - 74,8 [55,06; 90] vs 47,6 [24,5;59,8] pg/ml, respectively (p=0,03). CP values on ICU admission correlated with need for VS (r=0,54; p=0,02 respectively) and showed higher concentrations in patients requiring VS compared with those with stable haemodynamics [74,8 vs 47,6 pg/ml, p=0,03] respectively. CP correlated with duration of ICU stay(r=0,43; p   Conclusion: CP could add prognostic information in SCAP patients.
Ejection Fraction Improvement After Primary Prevention Defibrillator Implantation
Authors: Kristen K. Patton
Journal: Journal of the American College of Cardiology (2015)

Sudden cardiac death (SCD), arguably one of the most tragic causes of death, is estimated to cause more than 300,000 fatalities annually in the United States [(1)][1]. This complex underlying pathophysiology usually requires interaction between an abnormal substrate and a trigger leading to a