tbuckley/cabot-search huggingface dataset:
A randomized phase II p53 vaccine trial comparing subcutaneous direct administration with intravenous peptide-pulsed dendritic cells in high risk ovarian cancer patients
Authors: V. E. Herrin, M. S. Achtar, S. M. Steinberg, T. L. Whiteside, E. Wieckowski, M. Czystowska, C. Visus, J. A. Berzofsky, S. N. Khleif
Journal: Journal of Clinical Oncology (2007)

3011 Background: 50% of ovarian cancers carry a p53 mutation, most of which can lead to overexpression of the protein, providing a unique target for vaccine therapy. Preclinical data shows cytotoxic T-lymphocytes can be generated against wild-type peptide and can lyse tumor cells overexpressing p53. There are many methods of antigen delivery for cancer vaccines and very few comparative studies have been conducted to determine the best of these. Here we report findings for this completed study comparing two methods of vaccination. Methods: Eligible patients had Stage III, IV, or recurrent ovarian cancer and were clinically NED at study entry. Elevated CA-125 was allowed. HLA-A2.1 and overexpression of p53 were required. A wild-type epitope (264–272) with high HLA-A2.1 affinity was utilized for vaccination. Two techniques were randomly compared: subcutaneous (SQ) peptide admixed with ISA-51 and GM-CSF adjuvants or peptide-pulsed dendritic cells given intravenously (IV). Both arms received 6 million IU/m2 IL-2 SQ for ten days beginning with cycle 3. Elispot analysis was utilized to assess immunologic response, the primary endpoint. After reaching statistical significance, accrual to the more technically difficult IV arm was halted. Results: Of 21 patients enrolled, 20 have evaluable data points; 13 on the SQ arm and 7 IV. On the SQ arm, 9 of 13 (69%) patients had evidence for immunologic response. On the IV arm, 5 of 7 (71%) patients had an immunologic response. 42% on each arm experienced some grade III or IV toxicity (increased liver enzymes on the SQ arm and fatigue and lymphopenia on the IV arm), but only one patient disenrolled due to toxicity, a cardiac arrhythmia exacerbated by IL-2. Mean overall survival (to date) on the SQ arm is 70.4 months and on the IV arm is 72.9 months. Conclusions: The patients on this study were mostly heavily treated patients with short disease-free intervals, yet we demonstrated that immune responses can be generated against a wild-type protein epitope in a significant number of patients. Both vaccine approaches were similarly effective. This result should lead to a trial of early vaccination in high- risk patients to potentially delay or even prevent recurrence. No significant financial relationships to disclose.
The other NMDA antagonists, amantadine, memantine, dextromethorphan: Role in cancer therapeutics
Authors: E. E. Prommer
Journal: Journal of Clinical Oncology (2004)

8223 Background: .NMDA receptor antagonists are being increasingly used in pain management. Like Ketamine and methadone other NMDA receptor antagonists that exist such as amantadine, memantine, and dextromethorphan have the potential to be useful in cancer symptom management. Methods: medline search of all randomized controlled trials and clinical trials from 1966–2003 was performed for memantine, dextromethorphan and amantadine with attention to potential usefulness in symptom control. Results: There were 37 trials involving the use of dextromethorphan. All trials involved pain management. Types of pain included, postoperative pain, phantom limb pain, postherpetic neuralgia, diabetic neuropathy and one study involving cancer pain. Most trials studied postoperative pain. Dextromethorphan was most effective in postoperative pain, phantom limb pain and diabetic neuropathy. It was ineffective in cancer pain and postherpetic neuralgia. There were six studies involving amantadine, and all except one involved neuropathic pain and most used amantadine intravenously. The postoperative pain study showed no benefit. One neuropathic pain study showed no benefit over intravenous lidocaine, but two studies were able to show decreased pain with amantadine infusions, compared to placebo. The remaining two studies were done in 1983 and 1973 and there was no data available. One amantadine study showed benefit in patients with fatigue secondary to multiple sclerosis. Three studies involving memantine were found. One involved phantom limb pain and was negative for benefit, one study examined memantine in diabetic neuropathy and postherpetic neuralgia and found improved analgesia only in patients with diabetic neuropathy. Finally, one study in postoperative chronic pain showed no benefit for memantine. Conclusion: More controlled studies need to be done with these agents, as it is still unclear whether or not they have a role in the management of neuropathic pain. The effect of amantadine in cancer related fatigue should also be studied. No significant financial relationships to disclose.
Abstract 11930: Late Right Heart Failure During Continuous-Flow Left Ventricular Assist Device Support Adversely Affects Post-Transplant Outcome
Authors: Koji Takeda, Hiroo Takayama, Bindu Kalesan, Paolo C Colombo, Ulrich P Jorde, Melana Yuzefpolskaya, Donna M Mancini, Yoshifumi Naka
Journal: Circulation (2014)

Background: Right heart failure (RHF) is an unresolved issue during continuous-flow left ventricular assist device (LVAD) support. There are scarce data about post-transplant outcomes in patients complicated with late RHF during LVAD support. Objective: To assess whether development of late RHF during LVAD support adversely affected post-transplant survival. Methods: Between May 2004 and December 2013, 141 patients underwent cardiac transplantation after isolated LVAD support as a bridge to transplant at our center. Late RHF was defined as HF requiring medical interventions &gt;4 weeks after LVAD implantation. During the same study period, 3 patients were bridged to transplant with concurrent right ventricular assist device (RVAD) support. Results: The mean age of the study cohort was 54 ± 13 years, 81% were male, and 35% had an ischemic etiology. The mean duration of LVAD support before transplantation was 270 days. Twenty-three patients (16%) developed late RHF during waiting period. Of these, 6 required repeated readmissions due to RHF and 12 were supported with inotropic agents at the time of transplantation. Those patients were more likely to have higher creatinine (1.3 ± 0.67 vs. 1.6 ± 0.86, p = 0.08), higher blood urea nitrogen (23 ± 10 vs. 32 ± 16, p = 0.0019), and lower albumin (4.1 ± 0.47 vs. 3.8 ± 0.59, p = 0.0019) levels at the time of transplantation compared to patients who did not develop RHF. Overall post-transplant survival rate were 87%, 83%, 77% at 1, 3, and 5 years, respectively. The 3-year post-transplant survival was significantly worse in patients who developed late RHF (Figure: 87% vs. 61%, p&lt;0.0001). There were no early and late deaths in patients with RVAD support. Conclusions: Patients who develop late RHF during LVAD support have diminished post-transplant survival. The initiation of RVAD support may be warranted to improve renal function and nutrition status for these high-risk patients.
Pitfalls for detecting interleukin-33 by ELISA in the serum of patients with primary Sjögren syndrome: comparison of different kits
Authors: Elodie Rivière, Bineta Ly, Saida Boudaoud, Houria Chavez, Gaetane Nocturne, Philippe Chanson, Corinne Miceli Richard, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2015)

The recent interest for interleukin-33 (IL-33) in primary Sjogren syndrome (pSS) pathophysiology is due to three studies,1–3 which have shown an increase in IL-33 serum levels in patients with pSS compared with controls. IL-33 is a member of the IL-1 family which is released in case of cellular damage and acts as an alarmin; however, its role in pSS physiopathology remains unclear.

In the present study, we aimed to replicate the association described between IL-33 serum level and pSS diagnosis. For that purpose, we used Quantikine and Duoset ELISA (R&D Systems, Minnesota, USA) and Luminex (Milliplex HTh17, Merck, Darmstadt, Germany). The Quantikine and Luminex kits are validated for serum samples, while the Duoset is only validated for use with culture supernates (data from R&D). IL-33 serum levels were assessed in patients with pSS from the French multicentre prospective ASSESS cohort (Assessment of Systemic Signs and Evolution in Sjogren Syndrome, principal investigator: X …
The nitric oxide (NO) metabolites in monitoring and therapy of bronchial asthma
Authors: Svetlana Soodaeva, Igor Klimanov, Alexander Lisitsa, Elena Zaprudnova
Journal: European Respiratory Journal (2011)

The aim of the study was to investigate the efficacy of the treatment of bronchial asthma using the estimation of the dynamics of stable NO metabolites in exhaled breath condensate (EBC). These parameters was also investigated for the monitoring of airway inflammation in patients with stable bronchial asthma treated by GINA-2009 guideline.   Materials and methods:  158 outpatients were enrolled in the study. Group1 contains 48 children (8-12 y.o.); group 2 contains 52 adults with the exacerbation of moderate bronchial asthma (BA). The control group consisted of 58 healthy volunteers. The EBC was collected in all patients, as well as the TNN concentration in EBC was measured before and after the course of therapy by spectrophotometric method using the Griess reaction.   Results:  The statistically significant decrease of TNN concentration in EBC both in children and adults was demonstrated during the study (in 4.0 and 4.5 times respectively compared to baseline). There was no difference in this parameter between the children and the adult group. After the course of therapy it was shown the decrease of TNN level in EBC in 89.7% of patients in both groups (in 1.6 and 1.7 times respectively). However, the TNN level in EBC was strongly higher in patients with BA than in control.   Conclusion:  The measurement of TNN concentration in EBC can be used as a marker of airway inflammation in patients with moderate BA for the monitoring of patient9s status. During the course of therapy the statistically significant decrease of this parameter was demonstrated; that is strongly correlated with clinical status. So, the TNN level in EBC also can be considered as a sensitive marker of the efficacy of the therapy administered.
Improving the therapeutic value of DNA methylation inhibitors
Authors: M. K. Yu, W. Nie, F. A. Fitzpatrick
Journal: Journal of Clinical Oncology (2005)

2109 Background: 5′-Azacytidine is clinically approved for the treatment of patients with myelodysplastic syndrome. Although the drug is thought to act through mechanisms of inhibition in DNA methylation, cell death results do not commonly correlate with demethylation of tumor suppressors. The approved dose used for the treatment of patients with myelodysplastic syndrome likely causes cytotoxicity of the cells in which there had been a demethylation effect. In vitro, 5′-aza-2′-deoxycytidine, also a nucleoside analog, appears to be a DNA methylation inhibitor with a more potent gene re-expression profile than 5′-azacytidine. In order to better understand how best to utilize DNA methylation inhibitors, further characterization of their proposed mechanism of action is required. Effective combination therapy can then be tested clinically. Methods: HCT-116 cells are cultured in DMEM with 10% fetal calf serum and treated with vehicle, 5′-azacytidine, or 5′-aza-2′-deoxycytidine. These cells were chosen because DNA methyltransferase-1 and 3b knockout cell lines (Vogelstein laboratory) were available to serve as controls. Cell lysates are prepared and separated by SDS-PAGE. Transcripts of DNA-methyltransferase-1 were assessed with real-time PCR. DNA methyltransferase-1-DNA complexes were fractionated with a density gradient after drug treatments. Results: We show degradation of DNA methyltransferase-1 begins after 24 hours of treatment with 300nM of 5′-azacytidine. A comparable degradation of DNA methyltransferase-1 is only seen after treatment with 1μM of 5′-aza-2′-deoxycytidine. Activation of caspase 3 was not seen after drug treatment of the cells. Treatment of HCT-116 cells with 5′-azacytidine or 5′-aza-2′-deoxycytidine does not change levels of DNA methyltransferase-1 mRNA. Degradation of DNA-methyltransferase-DNA complexes occurs at a lower concentration of 5′-azacytidine compared to 5′-aza-2′-deoxycytidine treated cells. Conclusions: Using DNA methyltransferase-1 degradation as a measurement of effect of demethylation, 5′-azacytidine may be more potent than 5′-aza-2′-deoxycytidine. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmion
Promotion of Tumor Growth In Vivo by Antimacrophage Agents 2
Authors: R. Keller
Journal: JNCI Journal of the National Cancer Institute (1976)

Various attempts were made to assess the role of the mononuclear phagocyte system in tumor resistance of rats in vivo. The growth of sc inoculated, weakly immunogenic, carcinogen-induced, syngeneic tumor cells was modestly reduced by ip injection and, more impressively, by local injection of peptone-induced, activated, nonimmune macrophages. A single iv injection of silica particles or carrageenan on the day of sc tumor cell inoculation greatly enhanced tumor growth. When these agents had been given a few days before or after tumor cell inoculation, the tumor-promoting efficiency was distintly diminished or even cancelled. The enhancing effects of silica and carrageenan on tumor growth were nulified by the macrophage-stabilizing agent, poly-2-vinylpyridine N-oxide, To assess the in vivo consequences of silica administration, various cellular, biochemical, and functional macrophage parameters were determined at different intervals. Results indicated the complexity of events elicited after the mononuclear phagoycte system was damaged, which made the interpretation of such results difficult.
Adaptation and validation of the Hospital Anxiety and Depression Scale (HADS) to a cohort of patients in Buenos Aires, Argentina
Authors: N. Gercovich, D. Gercovich, F. Torrente, P. Lopez, D. Bortolato, P. Margiolakis, M. Morgenfeld, L. Rosell, G. Paoloski, J. Pollola
Journal: Journal of Clinical Oncology (2008)

20616 Background: The Hospital Anxiety and Depression Scale (HADS) is an instrument widely used to evaluate psychiatric symptomatology in patients diagnosed with cancer. However there is not a validated version of the scale in Spanish as yet. Objectives: The aim of this study is to calculate the reliability and validity indexes of a Spanish version of HADS in a sample of subjects from the city of Buenos Aires. Methods: Between 01/2006 And 12/2006 754 persons have been subjected to HADS: Group A: 155 oncological patients attending a psycho-oncological service, Group B: 267 oncological patients randomly selected from the waiting room of a center specialized in oncological pathologies, and Group C: 332 healthy citizens, 18 years and older, from the city of Buenos Aires. The reliability of the instrument was evaluated with the “test-retest” method. Every person taking place in the study signed an informed-consent form. The validity of the topics was estimated through the “item-subscale” relation and factorial analysis. The SCL-90’s anxiety and depression subscales were used as external criteria to calculate the concurrent validity. Finally, the instrument’s discriminative capacity was evaluated among the three groups. Results: The “test-retest” reliability presented Spearman correlation indexes close to 0.85. The internal consistency, calculated through the Cronbach α test was of 0.85 (total scale), 0.78 (anxiety) and 0.77 (depression). The results of the factorial analysis of the 2 factors were acceptable. Comparison with the SCL-90 subscales show elevated values of concurrent validity Using the Kruskal Wallis test, significant differences were found among the three groups regarding the anxiety subscale and important differences were observed between group A and the other two groups in the depression subscale. Conclusions: The study of the Spanish version of HADS in a cohort of patients from Buenos Aires has shown indicators that allow us to consider HADS as a reliable and valid measurement of oncological patients’ psychiatric symptomatology. No significant financial relationships to disclose.
T cell subsets: an immunological biomarker to predict progression to clinical arthritis in ACPA-positive individuals
Authors: L Hunt, E M Hensor, J Nam, A N Burska, R Parmar, P Emery, F Ponchel
Journal: Annals of the Rheumatic Diseases (2015)

Anticitrullinated protein antibody (ACPA)+ individuals with non-specific musculoskeletal symptoms are at risk of inflammatory arthritis (IA). This study aims to demonstrate the predictive value of T cell subset quantification for progression towards IA and compare it with previously identified clinical predictors of progression.103 ACPA+ individuals without clinical synovitis were observed 3-monthly for 12 months and then as clinically indicated. The end point was the development of IA. Naïve, regulatory T cells (Treg) and inflammation related cells (IRCs) were quantified by flow cytometry. Areas under the ROC curve (AUC) were calculated. Adjusted logistic regressions and Cox proportional hazards models for time to progression to IA were constructed.Compared with healthy controls (age adjusted where appropriate), ACPA+ individuals demonstrated reduced naïve (22.1% of subjects) and Treg (35.8%) frequencies and elevated IRC (29.5%). Of the 103 subjects, 48(46.6%) progressed. Individually, T cell subsets were weakly predictive (AUC between 0.63 and 0.66), although the presence of 2 T cell abnormalities had high specificity. Three models were compared: model-1 used T cell subsets only, model-2 used previously published clinical parameters, model-3 combined clinical data and T cell data. Model-3 performed the best (AUC 0.79 (95% CI 0.70 to 0.89)) compared with model-1 (0.75 (0.65 to 0.86)) and particularly with model-2 (0.62 (0.54 to 0.76)) demonstrating the added value of T cell subsets. Time to progression differed significantly between high-risk, moderate-risk and low-risk groups from model-3 (p=0.001, median 15.4 months, 25.8 months and 63.4 months, respectively).T cell subset dysregulation in ACPA+ individuals predates the onset of IA, predicts the risk and faster progression to IA, with added value over previously published clinical predictors of progression.
Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline
Authors: Lyndsay N. Harris, Nofisat Ismaila, Lisa M. McShane, Fabrice Andre, Deborah E. Collyar, Ana M. Gonzalez-Angulo, Elizabeth H. Hammond, Nicole M. Kuderer, Minetta C. Liu, Robert G. Mennel, Catherine Van Poznak, Robert C. Bast, Daniel F. Hayes
Journal: Journal of Clinical Oncology (2016)

To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer.A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations.The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens.In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences.
원저 : 진행성 간세포암에서 지속적 경구 Etoposide 와 Tamoxifen 의 치료효과
Authors: 김호영(Ho Young Kim), 이종인(Chong In Lee), 심광용(Kwang Yong Shim), 김용태(Yong Tai Kim), 김재권(Jae Gwom Kim), 김민수(Min Soo Kim), 백순구(Soon Ku Baik), 이동기(Dong Ki Lee), 권상옥(Sang Ok Kwon), 심영학(Young Hak Shim), 장우익(Woo Ick Jang)
Journal: Clinical and Molecular Hepatology (2000)

Aims :. This study evaluated the use and efficacy of chronic oral etoposide plus tamoxifen as a palliative treatment in 30 patients with far-advanced HCC in whom surgical resection, percutaneous ethanol injection or transarterial chemoembolization(TACE) was not possible. Methods : To be eligible for the study, patients had to have objectively measurable or evaluable tumors, adequate hematologic profiles and hepatorenal functions, had to be between 20 and 75 years of age, and had to have an ECOG performance status of less than or equal to 2. The treatment included etoposide, 50 mg/m2/day, taken orally for 21 days, and tamoxifen, 40 mg/day, taken orally for 21 days. Each cycle was repeated every 5 weeks. Results : Two patients(7%) achieved a partial response(PR) and 16 patients(53%) achieved a stable disease(SD) with a median time-to-progression of 5 months(range: 2-24). Median of patients survival with the response of PR or SD and those patients with the response of progressive disease(PD) was 10 months and 7 months, respectively(p=0.0004). Of the 20 patients with initial elevated serum alpha-fetoprotein(≥500 ng/ml), 9 patients(45%) experienced a significant(≥50%) decrease in their values after chemotherapy and all 9 patients achieved objective tumor response of more than or equal to SD. Among the 30 patients in the study, 10 patients(33%) achieved performance status improvements of grade according to the ECOG criteria and 6 patients(20%) experienced improvements of subjective symptoms, such as abdominal pain, abdominal fullness and anorexia. Conclusion : Based on our results, the use of chronic oral etoposide plus tamoxifen as a palliative treatment for the far-advanced hepatocellular carcinoma are beneficial. A randomized two-arm study may be warranted to validate the results of this study.(Korean J Hepatol 2000;6:41-51)