tbuckley/cabot-search huggingface dataset:
Lenalidomide Enhances Immune Checkpoint Blockade-Induced Immune Response in Multiple Myeloma
Authors: Güllü Görgün, Mehmet K. Samur, Kristen B. Cowens, Steven Paula, Giada Bianchi, Julie E. Anderson, Randie E. White, Ahaana Singh, Hiroto Ohguchi, Rikio Suzuki, Shohei Kikuchi, Takeshi Harada, Teru Hideshima, Yu-Tzu Tai, Jacob P. Laubach, Noopur Raje, Florence Magrangeas, Stephane Minvielle, Herve Avet-Loiseau, Nikhil C. Munshi, David M. Dorfman, Paul G. Richardson, Kenneth C. Anderson
Journal: Clinical Cancer Research (2015)

Abstract Purpose: PD-1/PD-L1 signaling promotes tumor growth while inhibiting effector cell–mediated antitumor immune responses. Here, we assessed the impact of single and dual blockade of PD-1/PD-L1, alone or in combination with lenalidomide, on accessory and immune cell function as well as multiple myeloma cell growth in the bone marrow (BM) milieu. Experimental Design: Surface expression of PD-1 on immune effector cells, and PD-L1 expression on CD138+ multiple myeloma cells and myeloid-derived suppressor cells (MDSC) were determined in BM from newly diagnosed (ND) multiple myeloma and relapsed/refractory (RR) multiple myeloma versus healthy donor (HD). We defined the impact of single and dual blockade of PD-1/PD-L1, alone and with lenalidomide, on autologous anti–multiple myeloma immune response and tumor cell growth. Results: Both ND and RR patient multiple myeloma cells have increased PD-L1 mRNA and surface expression compared with HD. There is also a significant increase in PD-1 expression on effector cells in multiple myeloma. Importantly, PD-1/PD-L1 blockade abrogates BM stromal cell (BMSC)-induced multiple myeloma growth, and combined blockade of PD-1/PD-L1 with lenalidomide further inhibits BMSC-induced tumor growth. These effects are associated with induction of intracellular expression of IFNγ and granzyme B in effector cells. Importantly, PD-L1 expression in multiple myeloma is higher on MDSC than on antigen-presenting cells, and PD-1/PD-L1 blockade inhibits MDSC-mediated multiple myeloma growth. Finally, lenalidomide with PD-1/PD-L1 blockade inhibits MDSC-mediated immune suppression. Conclusions: Our data therefore demonstrate that checkpoint signaling plays an important role in providing the tumor-promoting, immune-suppressive microenvironment in multiple myeloma, and that PD-1/PD-L1 blockade induces anti–multiple myeloma immune response that can be enhanced by lenalidomide, providing the framework for clinical evaluation of combination therapy. Clin Cancer Res; 21(20); 4607–18. ©2015 AACR.
Does CTLA-4 and CD-28 polymorphism affect the lung involvement in Turkish ankylosing spondylitis patients??
Authors: Fatmanur Karakose, Aylin Rezvani, Saime Turan, Omer Uysal, Muhammet Emin Akkoyunlu, Nazli Ezgi Ozkan, Mehmet Bayram, Hatice Sozgen, Fatih Yakar, Hatice Ozcelik, Murat Sezer, Mustafa Guler, Ilhan Yaylim, Levent Kart
Journal: European Respiratory Journal (2014)

Ankylosing spondylitis is a multisystemic disorder with ocular, pulmonary, and cardiovascular involvement. Data from AS patients who have amyloidosis, psoriasis suggest that immunologic or inflammatory mechanisms may be responsible for pathogenesis.Incidence of pulmonary involvement is 1 to 70%,but pathophysiology is still unknown.We aimed to address the relationship between CTLA4 and CD28 polymorphism in AS patients who have lung involvement.Enrolled were 80 controls and 89 AS patients diagnosed according to the Modified New York Criteria in the Physical Medicine and Rehabilitation Department of the Rheumatology Outpatient Clinic.CTLA4 and CD28 polymorphism analysis and clinical,radiological assessment were performed.  We found a correlation between HRCT findings and CD 28 gene polymorphism,but no significant association was detected between CTLA4-318,CTLA4-49 and CD28 genotypes and the clinical characteristics of the patients. All patients with the CD28 CC genotype had abnormal HRCT to a statistically significant degree(p=0.047)but no other correlation was found between CTLA 4, CD28 gene polymorphism, and PFTs and clinical characteristics.
Phase II trial of docetaxel: a new, highly effective antineoplastic agent in the management of patients with anthracycline-resistant metastatic breast cancer.
Authors: V Valero, F A Holmes, R S Walters, R L Theriault, L Esparza, G Fraschini, G A Fonseca, R E Bellet, A U Buzdar, G N Hortobagyi
Journal: Journal of Clinical Oncology (1995)

PURPOSE To determine the efficacy (objective response rate and duration of response and survival) and toxicity of docetaxel in patients with strictly defined anthracycline-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS Thirty-five patients with bidimensionally measurable MBC who had progressive disease while receiving anthracycline-containing chemotherapy were registered onto the phase II trial. Docetaxel was administered at a dose of 100 mg/m2 over 1 hour every 21 days. RESULTS Thirty-four patients were assessable for disease response; 18 (53%; 95% confidence interval [CI], 35% to 70%) achieved a partial response. The median times to disease progression and survival duration were 7.5 and 13.5 months, respectively, for responding patients. The median overall survival duration was 9 months. Two hundred eight cycles (median, five) of docetaxel were administered. Neutropenia with less than 500 cells/microL developed in 31 of 35 patients; it was complicated by fever in 30 (14%) of 208 cycles and in 18 (51%) of 35 patients, including one treatment-related death. Fluid retention was seen in 15 (43%) of 35 patients, including pleural effusions in 11 patients (31%). Moderate skin toxicity, asthenia, and myalgia were observed in 16%, 58%, and 37% of cycles, respectively. CONCLUSION Docetaxel has the highest reported antitumor activity in anthracycline-resistant MBC. High objective response rates were seen in patients with visceral-dominant involvement, multiple metastatic sites, or extensive previous therapy. Docetaxel is associated with severe but reversible neutropenia, asthenia, and cumulative dose-related fluid retention. Dexamethasone decreased the frequency and severity of skin toxicity and appeared to ameliorate fluid retention.
Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens
Authors: Ruben Niesvizky, Ian W. Flinn, Robert Rifkin, Nashat Gabrail, Veena Charu, Billy Clowney, James Essell, Yousuf Gaffar, Thomas Warr, Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, Liviu Niculescu, James Reeves
Journal: Journal of Clinical Oncology (2015)

The US community-based, phase IIIB UPFRONT trial was designed to compare three frontline bortezomib-based regimens in transplantation-ineligible patients with myeloma.Patients (N = 502) were randomly assigned 1:1:1 to 24 weeks (eight 21-day cycles) of induction with bortezomib-dexamethasone (VD; n = 168; intravenous bortezomib 1.3 mg/m(2), days 1, 4, 8, and 11 plus oral dexamethasone 20 mg, days 1, 2, 4, 5, 8, 9, 11, and 12 [cycles 1 to 4], or 1, 2, 4, and 5 [cycles 5 to 8]), bortezomib-thalidomide-dexamethasone (VTD; n = 167; bortezomib and dexamethasone as before plus oral thalidomide 100 mg, days 1 to 21), or bortezomib-melphalan-prednisone (VMP; n = 167; bortezomib as before plus oral melphalan 9 mg/m(2) and oral prednisone 60 mg/m(2), days 1 to 4, every other cycle), followed by 25 weeks (five 35-day cycles) of bortezomib maintenance (1.6 mg/m(2), days 1, 8, 15, and 22). The primary end point was progression-free survival.After 42.7 months' median follow-up, median progression-free survival with VD, VTD, and VMP was 14.7, 15.4, and 17.3 months, respectively; median overall survival was 49.8, 51.5, and 53.1 months, with no significant differences among treatments for either end point (global P = .46 and P = .79, respectively, Wald test). Overall response rates were 73% (VD), 80% (VTD), and 70% (VMP). Adverse events were more common with VTD than VD or VMP. Bortezomib maintenance was feasible without producing cumulative toxicity.Although all bortezomib-containing regimens produced good outcomes, VTD and VMP did not appear to offer an advantage over VD in transplantation-ineligible patients with myeloma treated in US community practice.
Surface Markers of Small Lymphocytes Appearing in Murine TA-3(St) Solid Tumors, Host Spleen, and Blood2
Authors: P. K. Lala, l. Kaizer
Journal: JNCI Journal of the National Cancer Institute (1977)

The presence of two surface markers, IgM for B-cells and θ-antigen for T-cells, was examined radioautographically on small lymphocytes appearing in subcutaneously grown TA-3 (Stockholm) line tumor in strain A mice, as well as in the spleen and blood at different days of tumor growth. IgM-positive cells were identified by surface labeling which resulted from a direct binding of 125l-labeled antimouse IgM raised in goats. Labeling of additional small lymphocytes resulting from an exposure of cells to anti-θ-antibody prior to incubation with 125l-labeled anti-lgM provided the incidence of θ-positive cells. Cells remaining unlabeled with the latter procedure were considered as double negative. When compared to the small lymphocytes in normal tissue (peritoneal) space, the proportion of IgM-positive cells declined, that of θ-positive cells remained unchanged, and that of double-negative cells increased markedly within the developing tumors. Absolute numbers of all three subsets within the tumor rose with increase in tumor age. Within the spleen, the proportion of IgM-positive cells remained unchanged, that of θ-positive cells declined, and that of double-negative cells increased substantially. Despite splenomegaly, the absolute number of θ-positive small lymphocytes in the spleen remained unchanged with time, while the remaining two subsets increased. In the circulation, the proportion of IgM-positive small lymphocytes showed an initial decline followed by a recovery, that of θ-positive cells declined, and that of double-negative cells increased significantly. The significance of an increase in the size of double-negative small lymphocyte populations within the tumor as well as other sites in the tumor-bearing host remains to be determined.
Enzymatic Susceptibility and Spontaneous Release of Human Melanoma Tumor-Associated Antigens2
Authors: Gary M. Stuhlmiller, H. F. Seigler
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Enzymatic Susceptibility and Spontaneous Release of Human Melanoma Tumor-Associated Antigens Get access Gary M. Stuhlmiller, Gary M. Stuhlmiller Search for other works by this author on: Oxford Academic PubMed Google Scholar H. F. Seigler H. F. Seigler Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 2, February 1977, Pages 215–221, https://doi.org/10.1093/jnci/58.2.215 Published: 01 February 1977 Article history Received: 11 May 1976 Accepted: 22 July 1976 Published: 01 February 1977
Simian Virus 40 (SV40) Production From SV40-Transformed Human Amnion Cells of Established Lines 2
Authors: Jørgen Fogh, James Loveless
Journal: JNCI Journal of the National Cancer Institute (1978)

Sixteen established cell lines of simian virus 40 (SV40)-transformed human amnion cells were examined for SV40 production. Many of these lines produced SV40 for extensive periods. Virus production had not ceased for 2 lines after 18 months, for 3 lines after 12 months, and for 3 lines at 3 months after recovery from "crisis". Three lines became virus-free in the first month, 1 line in the second month, 1 in the third month, and 1 in the fourth month, and 2 lines stopped virus production between 6 and 11 months after recovery. The virus titers were relatively low. Inclusion body-containing cells were infrequent. In contrast, in most cultures of SV40-transformed human fibroblasts rescued from crisis, no infectious virus was demonstrated, although exceptions have been reported. Virus was produced after heterokaryon formation of cells of the virus-free amnion lines with CV-1 cells in the presence of inactivated Sendai virus, as observed for SV40-transformed human fibroblasts. During the crisis period, some of the SV40-transformed amnion cells produced substantial amounts of virus. Titers decreased during the later periods of crisis. The most pronounced decrease in titers was in cultures from which established lines were recovered.
Hyperthermic Intraperitoneal Chemoterapy (Hipec) and Cytoreductive Surgery for Synchronous Peritoneal Carcinomatosis (Pc) from Gastric Cancer (Gc) : Results from a Single Center Experience
Authors: M. Amram, D. Benamran, G. Wirth, A.D. Roth, O. Huber
Journal: Annals of Oncology (2014)
Prognostic factors affecting survival in cases with lung cancer [A lung cancer mapping project in Turkey (LCMPT)]
Authors: Tuncay Goksel, Sultan Eser, Salih Z. Guclu, Mehmet Karadag, Aykut Cilli, Tevfik Ozlu, Metin Gorguner, Ugur Gonlugur, Fusun Topcu
Journal: European Respiratory Journal (2013)

Aim: To investigate survival and prognostic factors on survival in cases with lung cancer.  Method: LCMPT conducted by TTS-LPMSG included 7197 patients with primary lung cancer diagnosed in 2005. After 5 years follow up period, 4531 patients (63.0%) whose survival data could be obtained were included in this study. To estimate survival of patients, Kaplan Meier method was used. To define factors affecting survival, Log Rank test for univariate analysis and Cox regression test for multivariate analysis were used.  Results: The estimated mean survival was found as 16.9 months (95% CI: 16.4-17.4), median survival is 9.0 months (95% CI: 8.6-9.3) for all patients. The 5-year survival rate was 8.9%. The 5-year survival rates as histological types were 12.1% for squamous cell carcinoma (SSC), 10.7% for large cell (LC), 7.5% adenocarcinoma (AC), and 4.3% small cell (SC) (p  Conclusion: Patients with lung cancer have had still short survival; diagnosis at early stages is the most important prognostic factor.
Tar Yields of Cigarettes and Male Lung Cancer Risk&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C Vutuc, M Kunze
Journal: JNCI Journal of the National Cancer Institute (1983)

Of 252 male lung cancer patients, 248 or 98% were cigarette smokers, significantly (P less than .001) more than in the control group (526 = 64% of 839). In relation to the relative risks (RR) of never-smokers, the adjusted (for age, total years smoked, and average number of cigarettes smoked per day) lung cancer RR for smokers who had exclusively smoked cigarettes belonging to group II (15-24 mg tar/cigarette) was 10.4 (P less than .001); for smokers who had exclusively smoked cigarettes belonging to group III (greater than 24 mg tar/cigarette), it was 25.1 (P less than .001). The respective RR of smokers who had mainly smoked cigarettes belonging to group I (less than 15 mg tar/cigarette), group II, or group III were 10.9 (P less than .001), 20.6 (P less than .001), and 36.7 (P less than .001). After the differences in daily consumption were taken into account, the adjusted (for age and total years smoked) lung cancer RR for smokers who had consumed mainly cigarettes belonging to the various groups were the following: group II (11-20 cigarettes/day) compared to group III (11-20 cigarettes/day), RR = 0.6 (P less than .05); group II (greater than 20 cigarettes/day) compared to group III (greater than 20 cigarettes/day), RR = 0.8; group II (greater than 20 cigarettes/day) compared to group III (11-20 cigarettes/day), RR = 1.3 (P less than .001); group II (greater than 20 cigarettes/day) compared to group III (less than 10 cigarettes/day), RR = 7.8 (P less than .001); and group II (11-20 cigarettes/day) compared to group III (less than 10 cigarettes/day), RR = 2.5 (P less than .001).
Pulmonary function is associated with pulmonary artery systolic pressure in the general population: The Rotterdam study
Authors: Daan Loth, Lies Lahousse, Maarten Leening, Bouwe Krijthe, Janine Felix, Henning Tiede, Ardeschir Ghofrani, Oscar Franco, Bruno Stricker, Guy Brusselle
Journal: European Respiratory Journal (2013)

AIM: Pulmonary hypertension (PH) is a progressive and fatal disease with many different causes one of which is COPD. We aimed to investigate the association of pulmonary arterial systolic pressure (PASP) and FEV1, FVC and FEV1/FVC in the general population.

METHODS: This study was part of the Rotterdam Study, a prospective population-based cohort study among subjects aged 45 years and over. Spirometry was performed according to ATS/ERS-guidelines. Echocardiographic PASP was estimated following the American Society of Echocardiography guidelines; PASP = 4 x tricuspid regurgitation peak velocity ^2 + right atrial pressure (RAP, based on inferior vena cava diameter and inspiratory collapse). All analyses were adjusted for age, sex, smoking, left ventricular function, BMI, and cardiovascular medication use.

RESULTS: From the most recent cross-sectional examination of the Rotterdam Study, a total of 2,903 individuals had complete assessment of both spirometry and echocardiography (44% males, mean age 75 years). Using a 40 mmHg cut-off, 56 (1.9%) participants had an echocardiographic suspicion PH.

Using linear regression per 10% decrease, FEV1 % predicted was associated with a PASP increase of 0.5 mmHg (CI: 0.4; 0.7), similar to FVC % pred (0.5 mmHg, CI: 0.3; 0.7). Lastly, FEV1/FVC showed an association of 1.0 mmHg (CI: 0.6; 1.4) increase. After excluding participants with spirometry defined COPD, the associations persisted.

When analysed dichotomously, FEV1 % pred, FVC% pred and FEV1/FVC were associated with an increased risk of PASP over 40 mmHg.

CONCLUSION: In the general population, pulmonary function shows a clear association with PASP, even in persons free of COPD.
AKR1C3 is a biomarker of sensitivity to PR-104 in preclinical models of T-cell acute lymphoblastic leukemia
Authors: Donya Moradi Manesh, Jad El-Hoss, Kathryn Evans, Jennifer Richmond, Cara E. Toscan, Lauryn S. Bracken, Ashlee Hedrick, Rosemary Sutton, Glenn M. Marshall, William R. Wilson, Raushan T. Kurmasheva, Catherine Billups, Peter J. Houghton, Malcolm A. Smith, Hernan Carol, Richard B. Lock
Journal: Blood (2015)
Detecting undiagnosed COPD: Using routine primary care data to select and validate candidate variables for COPD risk prediction
Authors: Shamil Haroon, Rachel Jordan, Richard Riley, Robert Lancashire, Tom Marshall, Peymane Adab
Journal: European Respiratory Journal (2013)

Aim   To select and internally validate candidate variables to risk predict COPD in primary care.   Background   COPD is under-diagnosed in primary care. A validated algorithm could be used to identify patients who might benefit from spirometry.   Method   We used data on 17,719 COPD patients and 35,944 age/sex-matched controls, randomised in a 2:1 ratio to form derivation and validation samples. Candidate predictors were selected and adjusted ORs were estimated from a random intercept model. The AUC was estimated in the validation sample.   Results   Mean age in the derivation sample was 69.7 years and 51.8% were male. Smoking status, salbutamol use and dyspnoea were the strongest predictors. The model had an AUC of 0.875 (95% CI 0.87 to 0.88). A cutpoint of 0.3 yielded 86.6% sensitivity and 70.1% specificity.   Conclusions   Our interim model appears to be highly predictive of incident COPD and will be further developed and externally validated in a large screening trial (TargetCOPD).
Physical and sexual abuse and associated mental disorders among alcoholic inpatients
Authors: M Windle, R C Windle, D M Scheidt, G B Miller
Journal: American Journal of Psychiatry (1995)

The purpose of this study was to investigate the adult psychiatric correlates of childhood abuse among alcoholic inpatients.The 802 patients, who included 321 women, were admitted to one of five New York State alcohol treatment inpatient centers. Each patient was interviewed, and sexual and physical abuse history, DSM-III diagnosis, and other characteristics were recorded.The overall prevalence of reported childhood abuse was 59% for women and 30% for men. Family history of alcoholism was associated with higher levels of physical and sexual abuse. Gender differences in types of childhood abuse (i.e., sexual abuse only, physical abuse only, dual abuse) were evident; 49% of the women and 12% of the men reported sexual abuse (with or without physical abuse), 33% of the women and 24% of the men reported physical abuse (with or without sexual abuse), and 23% of the women and 5% of the men reported dual abuse. Abuse status, and especially dual abuse, was associated with higher rates of antisocial personality disorder and suicide attempts among women and men, with generalized anxiety disorder among women, and with major depression among men.The findings highlight the long-term associations between sexual and physical abuse and adult coexisting mental disorders among alcoholic inpatients. Addressing unresolved intrapsychic trauma associated with childhood abuse may increase the efficacy of treatment outcomes and reduce relapse rates among alcoholics.
Rapid Grain and Cell Counting for Cell Kinetic Studies: Brief Communication
Authors: Paul A. Bunn, Sharon S. Ford, Stanley E. Shackney
Journal: JNCI Journal of the National Cancer Institute (1977)

A commercially available bacterial colony counter has been adapted for the counting of radioautographic grains over individual cells in smears and for the counting of cells in histologic sections. For radioautographic grains, the correlation coefficients between counts obtained visually by 2 observers and between counts obtained visually and with the use of the instrument were similar (r = 0.999 and r = 0.998, respectively). The instrument counts were obtained more rapidly than the visual counts and were associated with less observer fatigue. Even though the performance of the instrument in counting cells in mouse bone marrow sections was less accurate than that in counting radioautographic grains, a good estimation of marrow cell number was obtained (r = 0.968). Data on bone marrow cellularity were obtained far more rapidly than those with semiquantitative methods.
Results in a tobacco consulting room in Albacete University Hospital in 2009
Authors: Francisco Javier Callejas Gonzalez, Javier Cruz Ruiz, Raul Godoy Mayoral, Ana Isabel Tornero Molina, Sergio Garía Castillo, Mariela Plenc Ziegler, Abel Martinez Garcia, Juan Pastrana Calderon, Rafaela Sanchez Simon-Talero, Juan Carlos Ceballos Romero
Journal: European Respiratory Journal (2012)

Introduction:  Results in a Tobacco Consulting Room in 2009.  Material and Methods : Retrospective descriptive analysis of the results obtained from patients who were attended in a Tobacco Consulting Room from 1 January to 31 December 2009 and subsequent follow-up to complete a year.  Results : 291 of 428 patients (51.2% male), mean age 46 years and mean cigarettes/day 27.5. Moderate-severe nicotine dependence (Fagerstrom 6.8) and high motivation (Richmond 8.11). Respiratory comorbidity: 12.1% COPD, 7.6% asthma, 11% OSAHS and 0.3% HOT; Cardiac: Ischemic Cardiopaty, 4.8% and Arrhytmia, 2.1%; CVRF: 30.9% dyslipidemia, 19.9% HT and 9.3% DM. 42.6% global psychiatric comorbidity, 37.5% depression and/or anxiety and 13.4% alcoholism. 22% without treatment, 44.6% NRT, 13.1% bupropion and 20.3% varenicline. Those who were treated pharmacologically, although non statistical significance, greater number of days of abstinence among who used varenicline than NRT or bupropion (59.3 vs. 46.7). 7.2% never got more than 24 hours abstinence. Overall of the 291 patients, treatment success (one year without smoking) in 31 (10.7%); Percentage rises to 24.8% if we don9t consider those who didn9t attend the second consultation.  Conclusions :  1.  70.8% didn9t start treatment (32% and 57%, first and second appointment respectively).  2.  Moderate-severe nicotine dependence and high motivation.  3.  Severe comorbidity, especially psychiatric, respiratory and CVRF.  4.  Greater number of days of abstinence among who used varenicline than NRT or bupropion (59.3 vs. 46.7).  5.  7.2% never got more than 24 hours abstinence.  6.  Overall treatment success 10.7%, amounting to 24.8% excluding those who don9t attend the second consultation.