tbuckley/cabot-search huggingface dataset:
Efficacy of docetaxel and prednisone in men with metastatic castration-resistant prostate cancer (mCRPC) exposed to prior ketoconazole (KC).
Authors: Gregory Russell Pond, Andrew J. Armstrong, Brian A. Wood, Lance Howard Leopold, Matt D. Galsky, Guru Sonpavde
Journal: Journal of Clinical Oncology (2012)

204 Background: The efficacy of docetaxel following exposure to androgen synthesis inhibitors such as KC or abiraterone acetate (AA) is unknown. Given the emerging use of pre-docetaxel AA and docetaxel’s inhibition of androgen signaling, we retrospectively evaluated the efficacy of every 3 week docetaxel with prednisone (DP) in mCRPC previously exposed to KC as compared to KC-naïve patients. Methods: A randomized phase II trial of men with mCRPC treated with DP+AT-101 (bcl-2 inhibitor) vs. DP+placebo was analyzed (stratified for pain and performance status). Both arms were combined for analysis as no significant differences were seen. Overall survival [OS], progression-free survival [PFS], objective response [ORR], pain and PSA response rates were estimated with and without prior KC. Results: Of 220 evaluable men, 40 (18.2%) received prior KC (median duration=2.0 months, maximum=31.1 months). These 40 men had less visceral disease (15% vs 28%), more prior radiotherapy (70% vs 51%), and increased prior radiological (38% vs 21%) or bone scan progression (55% vs 41%). Efficacy outcomes were not statistically different (table). After adjusting for baseline stratum and treatment group, prior KC did not appear to significantly change OS with DP-based therapy (HR 1.34, 95%CI: 0.86–2.09, p=0.20). Conclusions: Similar outcomes were observed in mCRPC treated with DP-based therapy with or without prior KC. Given the marginally inferior survival with prior KC, evaluation of docetaxel outcomes following AA is of clinical importance, given its more potent CYP17 inhibition. [Table: see text]
Persistent Effects of Intensive Glycemic Control on Retinopathy in Type 2 Diabetes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Follow-On Study
Journal: Diabetes Care (2016)

OBJECTIVES This study investigated whether the beneficial effects of intensive glycemic control and fenofibrate treatment of dyslipidemia in reducing retinopathy progression demonstrated in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study persisted beyond the clinical trial. RESEARCH DESIGN AND METHODS The ACCORD Study (2003–2009) randomized participants with type 2 diabetes to intensive or standard treatment for glycemia (A1C level at &amp;lt;6.0% [42 mmol/mol] vs. 7.0–7.9% [53–63 mmol/mol]), systolic blood pressure (&amp;lt;120 vs. 140 mmHg), and dyslipidemia (fenofibrate [160 mg] plus simvastatin or placebo plus simvastatin). ACCORD Eye Study participants, who had baseline and year 4 eye examinations and fundus photographs, were reexamined in the ACCORD Follow-On (ACCORDION) Eye Study (2010–2014) 4 years after the ACCORD trial closeout. The outcome measure was diabetic retinopathy progression of three or more steps on the Early Treatment Diabetic Retinopathy Study scale. RESULTS Diabetic retinopathy progressed in 5.8% with intensive glycemic treatment versus 12.7% with standard (adjusted odds ratio [aOR] 0.42, 95% CI 0.28–0.63, P &amp;lt; 0.0001), 7.5% with intensive blood pressure treatment versus 6.0% for standard (aOR 1.21, 95% CI 0.61–2.40, P = 0.59), and 11.8% with fenofibrate versus 10.2% with placebo (aOR 1.13, 95% CI 0.71–1.79, P = 0.60) in ACCORDION Eye participants (n = 1,310). CONCLUSIONS Prior intensive glycemic control continued to reduce diabetic retinopathy progression, despite similar A1C levels, when the ACCORD Study ended. This is the first study in people with type 2 diabetes of 10 years’ duration and established cardiovascular disease, unlike the newly diagnosed participants of the UK Prospective Diabetes Study, to demonstrate this effect. The benefit of fenofibrate, however, did not persist. Intensive blood pressure control had no effect.
Identifying cancer patients at high risk for chemotherapy-induced nausea and vomiting (CINV): the development of a prediction tool
Authors: G. Dranitsaris, A. Molasiotis, M. Clemons, E. Roeland, L. Schwartzberg, D. Warr, K. Jordan, P. Dielenseger, M.S. Aapro
Journal: Annals of Oncology (2016)
Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia: A Comparative Study of Flow Cytometry and Quantitative Real-Time Polymerase Chain Reaction (RQ-PCR).
Authors: Ashish K. Misra, Mary Sartor, Rosemary Sutton, Nicola C. Venn, Shamira Cross, Ken Bradstock, Murray Norris, Luciano Dalla-Pozza
Journal: Blood (2004)
MPTH-24. CYSTATHIONE β-SYNTHASE EXPRESSION IN ASTROCYTOMAS INCREASES WITH HISTOPATHOLOGICAL GRADE
Authors: Mirna Lechpammer, Krista Thongphanh, Kiarash Shahlaie, Syed Azeem, John Bishop, Evgeny Nudler, David Zagzag
Journal: Neuro-Oncology (2016)

Hydrogen sulfide (H2S) and other cysteine metabolites have been implicated in the growth and spread of astrocytomas. The aim of this study is to investigate cystathionine B-synthase (CBS; the brain’s main H2S producing enzyme) expression in astrocytomas and its correlation with histopathological grade. Twenty two adult patients (14 M / 8 F), who underwent surgical resection for newly diagnosed astrocytomas were retrospectively reviewed for CBS expression by immunohistochemistry (IHC). Patient age ranged from 26 to 77 years (mean 64 years). Staining scores were determined by multiplying the percentage of lesional cells staining with an intensity score of 1+, 2+, or 3+ (H-score; range: 0 – 300). CBS was expressed in 40% (2/5) of diffuse astrocytomas; 83% (5/6) of anaplastic astrocytomas and in 100% (11/11) of examined glioblastomas, with a higher staining intensity in psudopalisading tumor cells adjacent to necrosis. Mean H-score also differed in CBS expressing tumors according to their grade, yielding the lowest score of 40 in patients with grade 2 diffuse astrocytomas, compared to scores of 182 and 189 in patients with anaplastic astrocytomas and glioblastomas, respectively. Furthermore, 75% (6/8) of astrocytomas with high CBS expression score (200+) had loss of ATRX, regardless of the respective grade. In addition, all of these tumors also had high proliferative activity (Ki67 >20%). CBS IHC expression in astrocytomas did not correlate with their p53 status nor MGMT methylation. Our results show more intense CBS expression and presumptively higher H2S activity in astrocytomas with aggressive phenotypes, in keeping with the assumed role of cysteine metabolites in tumor progression and metastasis. Thus, our study suggests using cysteine metabolites as potential prognostic markers and therapeutic targets in astrocytoma treatment.
Ibrutinib, a BTK inhibitor used for treatment of lymphoproliferative disorders, eliminates both aeroallergen skin test and basophil activation test reactivity in allergic cancer patients receiving drug
Authors: Jennifer A. Regan, Adam M. Petrich, Melanie C. Dispenza, Shuo Ma, Leo I. Gordon, Bruce S. Bochner
Journal: Journal of Allergy and Clinical Immunology (2017)
A phase I study of silibinin in hormone refractory prostate cancer
Authors: T. Flaig, R. Agarwal, L.-J. Su, G. S. Harrison, D. L. Gustafson, L. M. Glode
Journal: Journal of Clinical Oncology (2005)

4698 Background: Silibinin is a polyphenolic flavonoid derived from the seeds of milk thistle. Silibinin has been used clinically in Europe and Asia for several decades to treat patients with chronic liver disease and after hepatotoxic ingestion. Preclinical data show antioxidant properties in addition to the inhibition of several mitogenic and survival signaling pathways including insulin-like growth factor receptor type 1, epidermal growth factor receptor, and NF kappa B. Methods: This is a preliminary report of a single institution phase I trial of Silibinin (Silybin-Phytosome TM) in patients with hormone refractory prostate cancer (HRPC). Patient eligibility included a PSA ≥ 1, Gleason score of ≤ 8, progressive disease despite hormonal therapy, and no radiation or investigational therapy in the 4 weeks preceding entry. The initial dose of Silibinin was 2.5 grams daily, in three divided doses. The next daily dose level was 5 grams, with subsequent increases by 5 gram increments. Once 3 patients were treated for a month at a particular dose level without dose limiting toxicity, all patients at lower doses were advanced to that level and new patients were started at the next dose level. Results: To date we have entered 18 patients in the Phase I portion of the study. Since an initial slow-release formulation did not result in measurable level of free Silibinin in blood, the original protocol was amended to administer Silibinin powder, as obtained from Indena, mixed with applesauce. Seven patients have now been registered on the newer protocol at up to 20g/day, with no significant adverse effects. An initial data review shows peak serum Silibinin levels of > 100 microM (approximately 50 μg/ml, a level found to be biologically active in animal studies) in some patients, with peak serum levels noted at 30 or 60 minutes in most patients. A large amount of inter-patient variability has been noted in peak serum levels. Conclusions: Oral Silibinin results in biologically relevant serum levels. Considerable variation was seen in peak serum levels between patients. This study will continue until the maximal tolerated dose of orally delivered Silibinin is established, before pursuing a phase II study in patients with HRPC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Indena
South African officials were “negligent and reckless” in transfer of vulnerable patients to cut costs
Authors: Pat Sidley
Journal: BMJ (2017)

At least 94 patients with mental illnesses and disabilities died in appalling circumstances after a contract between a private mental hospital and the Gauteng provincial government was cancelled last year.

Patients were transferred from Life Healthcare Esidimeni, a large private hospital, to 27 facilities run by non-governmental organisations according to the 60 page report by South Africa’s new Health Ombud, Malegapuru Makgoba.1 He was asked to investigate the deaths by health minister Aaron Motsoaledi when 36 deaths first came to light last year.

“Some of …
Endothelial Glycocalyx Degradation Is Associated with Bleeding, Thrombocytopathy, Endothelial Disruption and Leukocytosis in Acute Myeloid Leukemia.
Authors: Anne Mette Larsen, Eva Birgitte Leinøe, Pär Johansson, Henrik Birgens, Sisse Rye Ostrowski
Journal: Blood (2012)
Comparison of standard immunohistochemistry and automated quantitative immunohistochemistry for quantification of signaling proteins in archival Ewing sarcoma samples.
Authors: Mark A. Applebaum, Dafydd G. Thomas, Andrew Horvai, Elizabeth R Lawlor, Steven G. DuBois
Journal: Journal of Clinical Oncology (2013)

10045 Background: Targeted therapies are increasingly being evaluated for patients with Ewing sarcoma (EWS). Optimal strategies for quantifying key signaling proteins from paraffin-embedded material remain unclear. We sought to quantify tumor expression of IGF-1R, EGFR, and PTEN in EWS using two different methodologies. Methods: Decalcified paraffin-embedded tissue was obtained from 40 patients with EWS. 28 samples were obtained at time of diagnosis, 6 after initial chemotherapy, and 6 at time of relapse. Tumor was evaluated for the expression of IGF-1R, PTEN, and EGFR using standard immunohistochemistry (IHC) and automated quantitative analysis (AQUA) immunohistochemistry. Standard IHC results were categorized as low, medium and high expression based on a pathologist’s review. Expression by AQUA was measured as a continuous variable in arbitrary units. One sided ANOVA analysis was used to compare the mean AQUA expression for each analyte between categories of expression by IHC. Results: The mean age of patients was 15 years (range 1-49 yrs) at time of diagnosis. 68% were male and 66% had localized disease. Samples displayed a wide range of expression by AQUA: mean IGF-1R = 10702 (range 393 - 14424); EGFR = 2750 (range 672 – 9798); and PTEN = 2250 (range 251 – 6557). Mean IGF-1R expression by AQUA did not differ significantly between standard IHC expression categories (mean IGF-1R expression by AQUA for low IHC = 11255, medium IHC = 11070, high IHC = 11023; p = 0.98). Mean PTEN expression by AQUA was higher in the medium and high IHC categories (mean PTEN expression by AQUA for low IHC = 1229, medium IHC = 2715, high IHC = 2940; p = 0.064). Only two samples expressed EGFR by standard IHC. These samples qualitatively had higher AQUA expression levels, but there were too few samples for a reliable determination of statistical significance. Conclusions: AQUA provides a more dynamic range for each marker, though there was poor correlation with standard IHC results. Larger sample sets are needed to determine the optimal approach for quantifying signaling proteins in Ewing sarcoma.
The effect of VEGF on T cells from ovarian cancer patients and healthy individuals via VEGF receptor type 2.
Authors: F. Zagouri, A. Ziogas, N. Gavalas, M. Tsiatas, O. Tsitsilonis, E. Politi, C. Liakou, A. Karadimou, K. Arapini, E. Terpos, M. A. Dimopoulos, A. Bamias
Journal: Journal of Clinical Oncology (2011)

e15552 Background: The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis is well characterized; nevertheless, it is also a key element in promoting tumor evasion of the immune system by down-regulating dendritic cell maturation and thus T cell activation. We investigated the possible direct effect of VEGF on T cell activation and through which type of VEGF receptor (VEGFR) it exerts this effect. Methods: Circulating T cells from healthy donors (n=9) and ovarian cancer patients (n=5) were expanded in cultures with anti-CD3 and IL-2 with or without VEGF for 14 days, and the number of T cells was assessed. Cultured T cells were also tested for their cytotoxic activity against K562 and Daudi cell lines, in a standard 4-h 51Cr-release assay, and the expression of VEGFRs 1, 2, and 3 was assayed by flow cytometry, immunocytochemistry, and Western blotting. To assess the ability of activated T cells to secrete VEGF, levels in culture supernatants were measured by ELISA. Results: The addition of VEGF in cultures showed that concentrations above 1 ng/ml significantly reduced T cell proliferation (p=0.043 for comaprison with controls). The suppressive effect was dose-dependent from 1 to 10 ng/ml, after which there was a plateau of the inhibitory effect. Protein expression studies demonstrated that CD3+ T cells express VEGFR-2 on their surface upon activation. The direct suppressive effect of VEGF on T cell proliferation was reversed by anti-VEGFR-2 antibodies. This finding proves that the suppressive effect of VEGF on T cells is mediated by VEGFR-2. We also showed that VEGF at 5 ng/ml significantly reduced the cytotoxic activity of T cells against K562 and Daudi cells (p=0.042 for comparison with controls). Activated T cells secreted VEGF in the culture environment (mean value: 192 pg/ml). Nevertheless, these levels are well below those necessary to produce T cell suppression in culture (1 ng/ml). Conclusions: This study shows that VEGF directly suppresses T cell activation via VEGF receptor type 2. The levels shown to produce suppression in vitro (>= 1 ng/ml) are in concert to the level of VEGF in ascites, which predicted for a poor outcome (1.9 ng/ml) in a previous study (Bamias et al, Gynecol Oncol 2008).
High Dose Methylprednisolone and Rituximab Is an Effective Therapy in Advanced Refractory Chronic Lymphocytic Leukaemia Resistant to Fludarabine Therapy.
Authors: Moez Dungarwalla, Pamala Kanagasabapathy, Samar Kulkarni, Steve O. Evans, Unell Riley, Gareth J. Morgan, Daniel Catovsky, Claire E. Dearden, Estella Matutes
Journal: Blood (2007)
Development of an Acoustofluidic Platform for Rapid Basophil Enrichment
Authors: Chloe G. Rose, Filip Plazonic, Hywel Morgan, Efrem Eren, Xunli L. Zhang, Dario Carugo, Peter Glynne-Jones, Laurie C.K. Lau, Martyn Hill, Andrew F. Walls
Journal: Journal of Allergy and Clinical Immunology (2017)
Circulating chromogranin-a (CgA) as a useful marker in the diagnosis and follow up of neuroendocrine tumors (nets): An Italian multicenter observational study (cromAnet)
Authors: L. Dogliotti, F. De Braud, G. Delle Fave, E. Degli Uberti, P. Tomassetti, M. Gion, A. Leon, M. Torta, L. Borgna
Journal: Journal of Clinical Oncology (2006)

14091 The primary objective of this study was to validate the clinical significance of blood evaluation of CgA in NET patients at the diagnosis (PHASE I) and during 2 years of follow-up (PHASE II). From May 2003 to October 2004, 276 patients entered the study from 40 Italian centers: 270 were evaluable. All basal and every 3 months collected CgA blood samples were centrally measured in two reference laboratories (Orbassano-Turin and Venice) where ELISA (DAKO,Denmark) or IRMA (CIS-Schering, France) were performed to look at the correlation between the two methods and their sensitivity and specificity. Lab results at the baseline have been recently published (Leon et al., Intern. J. Biol. Markers, 2005). We are now collecting all the correlations between CgA and type and place of NETs; tumor bulk; metastatization; presence or not of specific syndrome;proliferation activity (Ki67); octreoscan; tumor specific markers. 223 patients (83%) had gastroenteropancreatic tumors, whereas 24 (9%) had medullary tyroid cancer, 16 (6%) Merkel cell carcinoma and 6 parathyroid NETs, pheochromocytoma, paraganglioma. Only 26% of GEP tumors presented with specific symptoms. At the entry in the study 58% of patients had a new diagnosis, 23% were in stable disease, whereas 18% had metastatic disease. According to the recent W.H.O. histologic classification (Solcia et al, 2000), 36% specific symptomatic patients had NE tumor, 57% well differentiated cancer and only 3% poor differentiated cancer, whereas 31% not symptomatic patients had NE tumor, 48% well differentiated and 16% poor differentiated cancer. This is the largest study worldwide performed on this topic and all the data about the correlation among all patient variables and CgA blood values will be ready in April 2006. Follow-up data will be evaluable next year. [Table: see text]
Changes in expression pattern of CEACAM1 in esophageal cancer: A factor of independent prognostic significance
Authors: Vassilios Papadopoulos, Uta Reichelt, Andreas Marx, Paulus Schurr, Jussuf Kaifi, Ronald Simon, Guido Sauter, Christoph Wagener, Jakob Izbicki
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3028 

Purpose: Carcinoembryonatic antigen-related-cell adhesion molecule 1 (CEACAM1) has recently been implicated in cancer development and progression. This study was performed to evaluate the prognostic relevance of CEACAM1 expression in esophageal cancer.

Experimental design: Immunhistochemical analysis using the monoclonal anti-CEACAM1-antibody 4D1/C2 was performed in a tissue microarray (TMA) constructed from paraffin-embedded tissues of patients with primary tumors (n=248), and matched nodal (n=145) as well as distant (n=45) metastases of the esophagus who underwent surgery between 1994 and 2004.

Results: CEACAM1 expression was detected in 141 of 248 (57%) esophageal cancers. Staining intensity was considered strong in 104 (74 %), and weak in 37 (26%) of the primary tumors. CEACAM1 expression findings of lymph node and distant metastases were strongly linked to the CEACAM1 findings in the respective primary tumors. CEACAM1 expression level was unrelated to patient survival. However, the staining pattern was prognostically relevant. Patients with apical expression (staining limited to the luminal surface of the cells) had a significant better overall survival (p=0.0076) as compared to tumors with a membranous pattern (staining surrounding the cells). Remarkably, the prognostic relevance of the staining pattern was linked to adenocarcinomas (p=0.0004), where it was independent from tumor stage (p=0.0064 in the subset of pT3-4 cancers), nodal stage (p=0.0032 in the subset of pN1) and grade (p=0.0286 in the subset of G3). In the subset of squamous cell carcinomas, apical expression pattern was not observed. In a multivariate Cox regression analysis including sex, age, tumor stage, differentiation grade and nodal status as covariates, next to tumor stage and nodal status, only the CEACAM1 expression pattern was a significant prognostic factor for survival (p =0.0112).

Conclusion: Loss of the physiological apical expression pattern of CEACAM1 is linked to poor prognosis in esophageal cancer. This change of the expression pattern might be useful to stratify patients with adenocarcinomas of the esophagus into low-risk and high-risk groups.
Perineural versus lymphovascular invasion: Which is a better marker for unfavorable biochemical outcomes following prostatectomy? Results from the Duke Prostate Center Database.
Authors: Abhay A Singh, Lionel Lloyds Banez, Leah Gerber, Stephen J. Freedland, Cary N. Robertson, Michael Ferrandino, Thomas Polascik, Philip John Walther, Judd W. Moul
Journal: Journal of Clinical Oncology (2012)

34 Background: Despite a substantial effort to study the clinical significance of perineural invasion in prostate biopsies (PNIb) its prognostic significance remains controversial. The limited data on perineural invasion in radical prostatectomy (RP) specimens (PNIp) suggests that biopsy specimens inadequately represent whole gland pathology thus rendering investigation of PNIp even more clinically relevant. While lymphovascular invasion in pathology specimens (LVIp) has been more rigorously investigated, studies have shown conflicting results. More importantly, there has been minimal comparison of PNIp and LVIp in the same cohort to determine which marker is the superior prognostic factor. Methods: We retrospectively analyzed data from 1611 men who underwent RP from 1999 to 2010 from the Duke Prostate Center database. We evaluated PNIp and LVIp as predictors of time to BCR by comparing hazard ratios (HR) and 95% confidence intervals (CI) using crude and adjusted proportional hazards regression models that included both variables and controlled for demographic and clinico-pathological covariates. Results: A total of 1304 (81%) men had PNIp while only 82 (5%) men had LVIp. On crude regression, both PNIp (HR=3.39; 95% CI=1.94-5.84; p&lt;0.001) and LVIp (HR=2.33; 95% CI=1.49-3.64; p&lt;0.001) were significant predictors of adverse BCR risk. After adjusting for clinico-pathological covariates, PNIp remained significantly associated with increased BCR risk (HR=1.85; 95%CI =1.04-3.31; p=0.04). Specifically, men with PNIp were 85% more likely to experience BCR relative to PNIp (-) men. In contrast, LVIp was not independently associated with BCR risk (p=0.23). Conclusions: In a cohort of men who underwent RP, PNIp is predictive of adverse BCR outcomes independent of clinicopathological parameters that include LVIp. Consequently, LVIp is a poor predictor of BCR risk. PNIp may thus provide additional prognostic information for men treated with RP and its inclusion in predictive nomograms requires study. Further analyses to determine if PNIp is likewise associated with metastasis and cancer-specific survival are warranted.
Enhancer of zeste homolog 2 (EZH2) expression in G1 -G2 Pancreatic Neuroendocrine Tumor (pNET)
Authors: R. Marconcini, P. Faviana, D. Campani, L. Galli, A. Antonuzzo, A. Falcone, S. Ricci
Journal: Annals of Oncology (2016)
Non-Cognate Cytotoxic T Cells Can Be Retargeted Against CD20 Positive Tumour Cells Using [Fab' × MHC Class I/Peptide] Conjugates.
Authors: Angela D Hamblin, Ben CR King, Ruth R French, Claude H Chan, Alison L Tutt, Philip M Savage, Peter W Johnson, Martin J Glennie
Journal: Blood (2010)
miR-425 regulates inflammatory cytokine production in CD4+ T cells via N-Ras upregulation in primary biliary cholangitis
Authors: Ryo Nakagawa, Ryosuke Muroyama, Chisato Saeki, Kaku Goto, Yoshimi Kaise, Kazuhiko Koike, Masanori Nakano, Yasuo Matsubara, Keiko Takano, Sayaka Ito, Masayuki Saruta, Naoya Kato, Mikio Zeniya
Journal: Journal of Hepatology (2017)