tbuckley/cabot-search huggingface dataset:
Peritoneal Macrophage Response to Leukemia L1210 in Syngeneic Mice 2
Authors: David Berd, Richmond T. Prehn
Journal: JNCI Journal of the National Cancer Institute (1977)

DBA/2 mice were inoculated ip with 103 live L1210 leukemia cells, which caused their death in 14 days. Three days after challenge, the peritoneal cavities of these animals contained about 6–8×106 nucleated cells, and by day 6 this amount increased to 25–50×106. Half the cells on day 3 and two-thirds on day 6 had a morphology typical of macrophages, many of which appeared activated. By tests of adherence and phagocytosis, they were confirmed to be macrophages. The remaining cells were intermediate between lymphocytes and macrophages, typical lymphocytes, polymorphonuclears, or L1210 cells. The ratio of the number of macrophages to the number of L1210 leukemia cells varied from 5:1 to 50:1. This ratio decreased to less than 1:1 on days 9 and 13 after challenge because of the rapid proliferation of the L1210 leukemia, but the absolute number of macrophages remained the same. Whole-body irradiation of mice with 400 R, 1 day before challenge, almost completely suppressed this macrophage response and resulted in a small but statistically significant shortening of survival time. A lower radiation dose, 200 R, only diminished the response and had a variable effect on survival. Athymic (“nude”) mice developed a macrophage response after an ip inoculation of L1210, although the magnitude was variable. It appeared then that the macrophage response was radiosensitive and T-cell-independent and may have had some controlling effect on the growth of L1210 in these syngeneic mice.
Immune monitoring technology primer: the enzyme-linked immunospot (Elispot) and Fluorospot assay
Authors: Sylvia Janetzki
Journal: Journal for ImmunoTherapy of Cancer (2015)

Elispot is a workhorse for functional analysis of single immune cells. Originally established for the enumeration of specific antibody-secreting B cells in 1983 [[1][1]], the technology has been expanded to the analysis of T cells, NK cells and monocytes. The assay is typically carried out in 96
A phase II, multi-center study of a new non-cytotoxic A<sub>3</sub> adenosine receptor agonist CF101, dose-finding (randomized blinded) in patients (pts) with refractory metastatic colorectal cancer
Authors: S. Stemmer, A. Shani, B. Klein, M. Silverman, I. Lorber, M. Farbstein, E. Shmueli, A. Figer
Journal: Journal of Clinical Oncology (2006)

13082 Background: The A 3 adenosine Gi protein-coupled receptor is highly expressed in malignant compared to normal cells. Activating the A 3 adenosine receptor (A 3 AR) with the highly selective non-cytotoxic agonist, CF101 (IB-MECA), inhibit of colon, prostate, melanoma, pancreatic and hepatocellular cancer growth in experimental animal models, via down-regulation of the Wnt and NF-κB signal transduction pathways. Oral CF101 has been shown to inhibit colon, prostate, melanoma, pancreatic and hepatocellular cancer growth in experimental animal models. Methods: A phase II dose-finding, randomized, blinded study of oral CF101 (0.1, 1&amp; 4 mg PO BID), was conducted to define activity and safety in heavily pre-treated metastatic colorectal cancer pts. From 6/1/2003–7/4/2004, 70 pts, median age 62 with measurable colorectal cancer, PS ≤2 were enrolled, 21 pts progressed after irinotecan and 49 pts after both irinotecan and oxaliplatin-based regimens. Results: The median time on treatment was 10.3 weeks. No objective response was observed; however, SD for 8 wks duration was achieved in 24 pts (34%), for 16 weeks in 8 pts (11%) and 2 pts were treated for more than 24 weeks. The median time to treatment progression was 72 days and for overall survival was 254 days without any significant difference among the 3 trial doses [8 survivors till today]. There were no obvious treatment related serious adverse events. Conclusions: The final results of the study show that CF101 is well tolerated and may stabilize disease for at least 2 months in 35% of the pts. The median survival time (8 months) compared with other targeted therapy investigated lately is encouraging. Combining CF101 with chemotherapy may be beneficial in the treatment of metastatic colorectal cancer. No significant financial relationships to disclose.
Smoking prevalence and relation to social factors in Don Benito-Villanueva area (Spain)
Authors: Juan Jose Garrido Romero, Francisco Javier Felix Redondo, Daniel Fernandez-Berges Gurrea, Francisca Lourdes Marquez Perez, Antonio Manuel Perez Fernandez
Journal: European Respiratory Journal (2013)

Introduction:  Smoking habit is a leading cause of mortality all around the world. Prevalence is going down in men, but increasing in woman in our country. Social factors associated to smoking are relevant to direct public health interventions.  Objetive:  To assess prevalence of smoking habit and its relationship to other social factors in Don Benito-Villanueva area (Spain).  Method:  2833 healthy people were randomly selected. Smoking was recorded as smoker, ex-smoker or never smoker. Number of cigarrettes/day, starting age and sociodemographic factors as age, gender, education, rural/urban area, worker/unemployed, exercise, alcohol use and immigrant/no was recorded too. Logistic regression test was used.  Results:  Prevalences are shown in Table 1.  Multivariate analisys for men and women are shown in Table 2.  Conclusions:  High prevalence of smoking is yet find out in our area. Stronger efforts has to be done and directed to certain population groups in order to improve results.
CD73 Is Associated with Poor Prognosis in High-Grade Serous Ovarian Cancer
Authors: Martin Turcotte, Kathleen Spring, Sandra Pommey, Guillaume Chouinard, Isabelle Cousineau, Joshy George, Gregory M. Chen, Deena M.A. Gendoo, Benjamin Haibe-Kains, Thomas Karn, Kurosh Rahimi, Cécile Le Page, Diane Provencher, Anne-Marie Mes-Masson, John Stagg
Journal: Cancer Research (2015)

The cell surface nucleotidase CD73 is an immunosuppressive enzyme involved in tumor progression and metastasis. Although preclinical studies suggest that CD73 can be targeted for cancer treatment, the clinical impact of CD73 in ovarian cancer remains unclear. In this study, we investigated the prognostic value of CD73 in high-grade serous (HGS) ovarian cancer using gene and protein expression analyses. Our results demonstrate that high levels of CD73 are significantly associated with shorter disease-free survival and overall survival in patients with HGS ovarian cancer. Furthermore, high levels of CD73 expression in ovarian tumor cells abolished the good prognosis associated with intraepithelial CD8(+) cells. Notably, CD73 gene expression was highest in the C1/stromal molecular subtype of HGS ovarian cancer and positively correlated with an epithelial-to-mesenchymal transition gene signature. Moreover, in vitro studies revealed that CD73 and extracellular adenosine enhance ovarian tumor cell growth as well as expression of antiapoptotic BCL-2 family members. Finally, in vivo coinjection of ID8 mouse ovarian tumor cells with mouse embryonic fibroblasts showed that CD73 expression in fibroblasts promotes tumor immune escape and thereby tumor growth. In conclusion, our study highlights a role for CD73 as a prognostic marker of patient survival and also as a candidate therapeutic target in HGS ovarian cancers.
Nonspecific Life Shortening in Male Mice Exposed to the Mammary Tumor Agent<xref ref-type="fn" rid="FN2">2</xref>
Authors: John B. Storer
Journal: JNCI Journal of the National Cancer Institute (1966)

Lifespan, gross tumor incidence, and body weight changes were measured in reciprocal hybrids between mouse strains C3H/HeJ, females of which transmit the milk-borne mammary-tumor-inciting virus to their progeny, and C57BL/6J, a strain free of the virus. In the hybrid males, in which mammary tumors do not influence longevity, the population exposed to the virus through their C3H/HeJ mothers showed a significantly lower mean lifespan than the reciprocal hybrids nursed by C57BL/6J mothers. The curves of distribution of deaths by age were very similar for the two groups with an apparent “shift to the left” (uniformly earlier deaths) in the virus-exposed group. Because of the experimental design certain alternative explanations could not be excluded, but it was considered most likely that the life-shortening was due to a nonspecific deleterious effect of the virus which resulted in either premature aging or accelerated aging.
Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma: a multicenter phase II study.
Authors: G Stoter, S Aamdal, S Rodenhuis, F J Cleton, S Iacobelli, C R Franks, R Oskam, E Shiloni
Journal: Journal of Clinical Oncology (1991)

Twenty-five assessable patients with metastatic melanoma have been entered in a multicenter phase II study of two induction cycles of human recombinant interleukin-2(IL2), 18 x 10(6) IU/m2/d continuous intravenous (IV) infusion on days 1 to 5 and days 12 to 17. Dacarbazine (DTIC), 850 mg/m2 IV bolus was given on day 26. The cycle was repeated at 5 weeks. Maintenance therapy was scheduled 3 weeks after the completion of induction treatment, consisting of IL2, 18 x 10(6) IU/m2/d for 5 days alternating with DTIC, 850 mg/m2 IV every 3 weeks, for a total of 18 weeks. Six patients responded (24%); two complete and four partial. Stable disease was seen in five patients. None of the six patients with more than two sites of metastases responded. Maximum response was observed in the first 3 months of treatment. Progression-free periods of 6 months and longer were seen in the two complete responders (8 and 17+ months), in two of the four partial responders (7 and 12+ months), and in three of the five patients with stable disease (9+, 15, and 17+ months). Toxicity included fever, skin rash, fatigue, anorexia, and diarrhea in most patients. Two patients had a weight gain of more than 10%. Eight patients needed intensive care for the observation and treatment of a myocardial injury (one patient), ventricular tachycardia (one), hypotension and oliguria (four), and sepsis (two). Sequential treatment with IL2 and DTIC appears to be effective but not clearly better than could be expected of IL2 alone.
CD4+ T-Cell Immune Response to Large B-Cell Non-Hodgkin’s Lymphoma Predicts Patient Outcome
Authors: Stephen M. Ansell, Mary Stenson, Thomas M. Habermann, Diane F. Jelinek, Thomas E. Witzig
Journal: Journal of Clinical Oncology (2001)

Previous studies in patients with non-Hodgkin's lymphoma (NHL) and other malignancies have suggested that the presence of host infiltrates in the tumors of these patients may predict a better outcome. This study was undertaken to determine the prognostic importance of the presence of T cells in the biopsy specimens of patients with B-cell NHL.Seventy-two patients with diffuse large B-cell NHL were prospectively evaluated at a single institution between 1987 and 1994. The percentage of CD3+, CD3+/HLA-DR+, CD4+, CD8+, and natural killer cells was determined by flow cytometry in the pretreatment diagnostic biopsy specimen and correlated with patient outcome.An increase in the percentage CD4+ T cells in the pretreatment tumor biopsies significantly correlated with patient outcome. The percent of CD4+ T cells was also highly correlated with CD3+/HLA-DR+, CD45RO+, and low L-selectin (CD62L) expression, indicating that the CD4+ T cells are activated memory T-helper cells. Those patients with increased numbers of CD4+ T cells, compared with other patients, had a significantly longer 5-year failure-free survival (72% v 43%, respectively; P =.04), as well as a significantly longer 5-year overall survival (65% v 38%, respectively; P =.05). When evaluated in a multivariate model, the International Prognostic Index and more than 20% infiltrating CD4+ T cells in the pretreatment biopsy were significant independent predictors of relapse-free and overall survival.The presence of increased numbers of activated CD4+ cells in the area of B-cell diffuse large-cell NHL predicts a better prognosis. This finding provides a strong rationale for the investigation of cellular immunotherapy in B-cell NHL.
Abstract 14551: Isoproterenol Induced Protein Phosphatase2Ce Up-Regulation Suppresses Cardiac Contraction
Authors: Toru Akaike, Gang Lu, Yibin Wang, Hongmei Ruan
Journal: Circulation (2011)

Protein phosphatase 2Ce (PP2Ce) is a novel serine/threonine protein phosphatase specifically targeted to sarcoplasmic reticulum (SR) membrane in cardiomyocytes. PP2Ce has a potent activity towards ...
Sputum biomarkers in stable COPD
Authors: Imre Barta, Balazs Antus
Journal: European Respiratory Journal (2011)

Characterization of the COPD proteome could help early diagnosis of the disease and aid the development of specific treatment options. The aim of this study was to detect sputum biomarkers characteristic for COPD.  Induced sputum was collected from 19 stable COPD patients (GOLD I-III, ex-smokers, mean age 62 years, pack year 52, FEV 1  64% predicted, FEV 1 /FVC 50%) and 19 healthy controls (mean age 62 years, pack year 29, FEV 1  110% predicted, FEV 1 /FVC 77%). CRP level (9.8mg/L vs. 5.1mg/L) and total sputum cell number (3.5×10 6  vs. 1.3×10 6 ) were significantly different between the two groups.  Sputum supernatants were subjected to cytokine antibody microarray analysis. Of the 120 cytokines investigated 96 was detectable above background level in the majority of samples. A greater subset of factors was down regulated while a smaller subset was up regulated in COPD. 14 cytokines exhibited a difference of at least 50% in relative expression level. IL-6, IL-1α, GRO and GROα expression was significantly different (p
Real time polymerase chain reaction (RT-PCR) based rapid detection of multi-drug resistant (MDR) mycobacterium tuberculosis (MTB)
Authors: T.K. Jayalakshmi, Mansi Rathore, Girish Pai, Dattatray Joshi
Journal: European Respiratory Journal (2011)

Objective:  Rapid confirmation of diagnosis of MTB and MDR-MTB in clinical samples by RT PCR and Melting Curve Analysis (MCA).   Introduction:  TB is one of the leading causes of mortality in world. An extremely worrisome aspect of MTB is the recent rise in MDR- MTB cases in several countries. The culture based diagnostic procedures take weeks to detect TB and its drug resistant variants. In developing countries this delay could compromise efforts to interrupt TB transmission. There is, therefore, intense interest to develop rapid and precise molecular diagnostic methods.   Methods:  DNA was extracted from sputum or body fluids of about 100 patients suspected of TB. MTB diagnosis was confirmed by RT PCR amplification and subsequent melting curve analysis, using IS6110 specific primers on Lightcycler480 (Roche Inc). For MDR MTB diagnosis hydrolysis probes were used to genotype mutations in rpoB and katG genes, associated with resistance to rifampin (RIF) and Isoniazide (INH) respectively.The data obtained from culture and molecular methods was compared.   Results:  MTB diagnosis was confirmed by RTPCR with 100% sensitivity on sybrgreen format. For detection of MDR, complete agreement between diagnoses from RT-PCR and Culture was observed in 38 cases out of 40 cases. 2 false positive for RIF resistance were was observed. No false positive or false negative cases were observed for resistance to INH in this study.   Conclusions:  RT PCR based assay with MCA has considerable promise for confirmation of diagnosis of MTB and MDR MTB. Development of more specific probes can further improve its diagnostic potential.
Incidence of Spontaneous Tumors in CD&lt;sup&gt;(R)&lt;/sup&gt;-1 HaM/ICR Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Dean H. Percy, Albert M. Jonas
Journal: JNCI Journal of the National Cancer Institute (1971)

In a study of the incidence of spontaneous neoplasms in 1,000 consecutive necropsies of CD(R)-1 HaM/lCR mice, the most common lesions in decreasing order of frequency were lymphoreticular, mammary, and pulmonary tumors, osteogenic sarcomas, hemangiosarcomas, and renal and hepatic tumors. The incidence of tumors per 100 animals rose with increasing age from less than 1/100 mice of the youngest age group to 50/100 in mice over 20 months of age.
Announcement: Heterocellular signalling and crosstalk in the heart in ischaemia and heart failure: to be published in May, 2014
Authors: E. Hirsch, R. Nagai, T. Thum
Journal: Cardiovascular Research (2013)

Cardiovascular Research publishes Focus review issues devoted to a specific research topic. These issues contain a number of expert reviews, and part of each issue is reserved for original research papers. All papers are subjected to the normal peer review process (an editorial decision is usually made within 22 days of receipt of any manuscript).

A Focus issue on …
Emergence in Brazil of methicillin-resistant Staphylococcus aureus isolates carrying SCCmecIV that are related genetically to the USA800 clone
Authors: O.P. de Miranda, M.C. Silva-Carvalho, A. Ribeiro, F. Portela, R.P. Cordeiro, N. Caetano, C.F.L. Vidal, A.M.S. Figueiredo
Journal: Clinical Microbiology and Infection (2007)
Daclizumab Improves Asthma Control in Patients with Moderate to Severe Persistent Asthma
Authors: William W. Busse, Elliot Israel, Harold S. Nelson, James W. Baker, B. Lauren Charous, Donald Y. Young, Vladimir Vexler, Richard S. Shames
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Airway inflammation in asthma is associated with increased activated CD25(+) T cells, IL-2, and soluble IL-2 receptors (IL-2Rs).A randomized, double-blinded, placebo-controlled study was used to evaluate the safety and efficacy of daclizumab, a humanized IgG1 monoclonal antibody against the IL-2R alpha chain (CD25) of activated lymphocytes, in adults with moderate to severe persistent asthma.Patients with obstructive pulmonary functions, despite inhaled corticosteroids (ICS), were switched to equivalent dose inhaled triamcinolone acetate acetonide (TAA). Patients dependent on ICS were randomized (3:1) to daclizumab (intravenous loading dose, 2 mg/kg, then 1 mg/kg) or placebo every 2 weeks, added to stable-dose TAA through Week 12 (Treatment Period 1). Over Weeks 12-20 (Treatment Period 2), patients tapered TAA while on the study drug, and were followed for 16 weeks off the study drug.Among 115 evaluable patients (88 daclizumab, 27 placebo), groups had similar age, disease duration, and length of ICS use. During Treatment Period 1, daclizumab improved FEV(1) (daclizumab, 4.4 +/- 1.80% vs. placebo, 1.5 +/- 2.39%; P = 0.05), and reduced daytime asthma symptoms (P = 0.018) and short-acting inhaled beta(2)-agonist use (P = 0.009). Daclizumab treatment prolonged time to exacerbation (P = 0.024). Adverse events were evenly distributed between groups, although there were more serious adverse events in the patients treated with daclizumab.Daclizumab improved pulmonary function and asthma control in patients with moderate to severe chronic asthma inadequately controlled on ICS. The mechanism of action likely involves inhibition of proinflammatory cytokine generation by IL-2R blockade in activated T cells. Clinical trial registered with www.clinicaltrials.gov (NCT00028288).
Testicular germ cell tumors and human immunodeficiency virus infection: a report of 26 cases. Italian Cooperative Group on AIDS and Tumors.
Authors: D Bernardi, R Salvioni, E Vaccher, L Repetto, N Piersantelli, B Marini, R Talamini, U Tirelli
Journal: Journal of Clinical Oncology (1995)

PURPOSE Besides tumors that are diagnostic of AIDS, such as non-Hodgkin's lymphoma, Kaposi's sarcoma, and invasive carcinoma of the cervix, other tumors have been described in the human immunodeficiency virus (HIV) setting. Some case reports on testicular cancer in HIV-infected patients have appeared in the literature. We present a retrospective study on 26 cases of testicular germ cell tumors (TGCTs) observed within the Italian Cooperative Group on AIDS and Tumors (GICAT) between November 1986 and September 1994. PATIENTS AND METHODS Twenty-six patients with TGCT and HIV-infection from the GICAT were retrospectively analyzed. RESULTS Fourteen patients had seminoma and 12 had nonseminoma. Four patients underwent only orchidectomy, one patient received only chemotherapy, nine patients were treated with postsurgical chemotherapy, 10 patients (38%) received postsurgical radiotherapy, one patient received postsurgical chemotherapy plus radiotherapy, and one patient was lost for follow-up evaluation immediately after diagnosis. The complete response (CR) rate was 95%. Relapse occurred in 32% of patients. The median follow-up time was 33 months. The mortality rate was 37%. Causes of death were neoplasia in three of nine patients, AIDS in five of nine patients, and fortuitous event in one of nine patients. The overall 3-year survival rate was 65%, and the 3-year disease-free survival rate was 65%. Severe hematologic toxicity was observed in seven of 15 patients. CONCLUSION HIV-infected patients with testicular cancer should be offered standard oncologic therapy, irrespective of their HIV status, since the majority can be cured of their tumor and have a good quality of life. Use of concomitant prophylaxis for opportunistic infections is recommended.
Management of Minor Medical Problems and Trauma: General Practice or Hospital?
Authors: Paul Myers
Journal: Journal of the Royal Society of Medicine (1982)

An assessment of the problems for which 1000 consecutive patients attended an accident and emergency department of a district general hospital showed that 54.2% could have been treated by general practitioner. Amongst 150 patients attending hospital for minor problems between the hours of 09:00 and 19:00 on weekdays, the main reason given for not going to a GP was their impression that only in hospital could the required treatment be provided. A postal survey of 50 GPs found that they tended to avoid regularly handling certain specified minor problems which often present to hospital. The current trend away from the community management of such problems is discussed. It is suggested that improving patient education and GPs' incentives, while decreasing list sizes and expanding the primary care team, may encourage the management by GPs of trivial trauma and minor medical problems.
Pseudomonas aeruginosa causes endoplasmic reticulum stress and loss of tight junctions (TJ) in primary bronchial epithelial cells (PBEC)
Authors: Emily F.A. van 't Wout, Annemarie van Schadewijk, Jan Stolk, Pieter S. Hiemstra
Journal: European Respiratory Journal (2012)

P.aeruginosa  has been shown to decrease epithelial barrier function by disrupting TJ, a process mediated by secreted virulence factors. In  C.elegans ,  P.aeruginosa  was shown to induce XBP-1 splicing (XBP1spl), a key event in endoplasmic reticulum (ER) stress. Moreover, patients with ER stress-associated lung diseases, like CF and COPD, show clinical deterioration after  P.aeruginosa  infection. We hypothesize that  P.aeruginosa  induces ER stress accompanied by loss of TJ, which is exaggerated in ER stress sensitized epithelial cells.  PBEC were exposed to conditioned medium of  P.aeruginosa  strain PAO1 (PAO1-CM) and/or thapsigargin (Tg; chemical ER stress inducer). PAO1-CM caused a time- and dose-dependent ER stress response with a maximal 11.9-fold increase (±7.8;p  PAO1-CM induces ER stress in PBEC which is associated with altered epithelial barrier function. Tg-induced ER stress increases the response to PAO1-CM. These mechanisms may contribute to the disease progression observed after  P.aeruginosa  infection.  This study was supported by a grant from the Netherlands Asthma Foundation (grant number: 3.2.08.032).