tbuckley/cabot-search huggingface dataset:
Expression of lncRNAs in Low-Grade Gliomas and Glioblastoma Multiforme: An In Silico Analysis
Authors: Brian J. Reon, Jordan Anaya, Ying Zhang, James Mandell, Benjamin Purow, Roger Abounader, Anindya Dutta
Journal: PLoS Medicine (2016)

Background Each year, over 16,000 patients die from malignant brain cancer in the US. Long noncoding RNAs (lncRNAs) have recently been shown to play critical roles in regulating neurogenesis and brain tumor progression. To better understand the role of lncRNAs in brain cancer, we performed a global analysis to identify and characterize all annotated and novel lncRNAs in both grade II and III gliomas as well as grade IV glioblastomas (glioblastoma multiforme [GBM]). Methods and Findings We determined the expression of all lncRNAs in over 650 brain cancer and 70 normal brain tissue RNA sequencing datasets from The Cancer Genome Atlas (TCGA) and other publicly available datasets. We identified 611 induced and 677 repressed lncRNAs in glial tumors relative to normal brains. Hundreds of lncRNAs were specifically expressed in each of the three lower grade glioma (LGG) subtypes (IDH1/2 wt, IDH1/2 mut, and IDH1/2 mut 1p19q codeletion) and the four subtypes of GBMs (classical, mesenchymal, neural, and proneural). Overlap between the subtype-specific lncRNAs in GBMs and LGGs demonstrated similarities between mesenchymal GBMs and IDH1/2 wt LGGs, with 2-fold higher overlap than would be expected by random chance. Using a multivariate Cox regression survival model, we identified 584 and 282 lncRNAs that were associated with a poor and good prognosis, respectively, in GBM patients. We developed a survival algorithm for LGGs based on the expression of 64 lncRNAs that was associated with patient prognosis in a test set (hazard ratio [HR] = 2.168, 95% CI = 1.765–2.807, p < 0.001) and validation set (HR = 1.921, 95% CI = 1.333–2.767, p < 0.001) of patients from TCGA. The main limitations of this study are that further work is needed to investigate the clinical relevance of our findings, and that validation in an independent dataset is needed to determine the robustness of our survival algorithm. Conclusions This work identifies a panel of lncRNAs that appear to be prognostic in gliomas and provides a critical resource for future studies examining the role of lncRNAs in brain cancers.
Maintenance of the suppressed level of serum testosterone by administration of three-monthly formulations of luteinizing hormone-releasing hormone agonists at six-month intervals in Japanese patients with prostate cancer: A prospective study.
Authors: Y. Fujii, S. Yoshida, M. Yokoyama, Y. Iimura, N. Numao, K. Saito, F. Koga, H. Masuda, S. Kawakami, K. Kihara
Journal: Journal of Clinical Oncology (2011)

159 Background: Treatment with an LH-RH agonist is a standard alternative to surgical castration for prostate cancer patients. The serum testosterone level is kept at castrate levels continuously during LH-RH agonist therapy in almost all patients (Fujii Y, BJU Int 2008). LH- RH agonists, however, are more expensive than surgical castration, with drugs costing between US $300 and $500 per month in Japan. Recent studies suggest that 3-monthly formulations of LH-RH agonists suppress the serum testosterone levels far longer than the 3-month dosing interval. Methods: A total of 43 Japanese patients with prostate cancer who were treated with 3-monthly LH-RH agonists (23 with 11.25mg leuprolide, and 20 with 10.8 mg goserelin) for one year or longer and whose testosterone levels were kept at castrate level (defined as &lt; 50 ng/dL) were entered into this prospective, longitudinal study. After entry, the 43 men received the same 3-monthly LH-RH agonists at 6-month intervals, and had serum LH and testosterone tests performed at 3-month intervals. Bicalutamide was combined with the LH-RH agonists in 12 of the patients. Results: At entry, median patient age was 74 years (range 59 to 89), median duration of LH-RH agonists treatment was 26 months (12 to 125), and median LH and testosterone levels were &lt;10 ng/dL (&lt;10 to 60) and 5 ng/dL (&lt;5 to 18), respectively. The 43 patients received a total of 162 administrations (median 5, range 1 to 6) of the LH-RH agonists at 6-month intervals, and had a total 335 hormonal tests (median 10, range 2 to12) performed during the median followup period of 30 months. Serum LH and testosterone levels were kept suppressed during the treatment. Of the 43 patients, two had serum testosterone just above the castrate level (54 and 56 ng/dL) once each among their 12 and 8 hormonal assays, respectively. Conclusions: Administration of 3-monthly LH-RH agonists, either leuprolide or goserelin, at 6-month intervals could maintain the castrate level of serum testosterone at least in Japanese prostate cancer patients who have received LH-RH agonists treatment for one year or longer. No significant financial relationships to disclose.
Andrew Wakefield calls Trump “on our side” over vaccines after meeting
Authors: Owen Dyer
Journal: BMJ (2016)

Anti-vaccine advocates across the US are optimistic about the prospect of one of their own occupying the Oval Office, after it emerged last month that the most famous vaccine critic in the US, Andrew Wakefield, met with Donald Trump before the election, leading a delegation of vaccine activists.

“For the first time in a long time, I feel very positive about this, because Donald Trump is not beholden to the pharmaceutical industry,” Wakefield told the US medical news website Stat last week. Wakefield was struck off as a doctor in the UK in 2010 for deliberately falsifying research to suggest that the measles-mumps-rubella (MMR) vaccine caused autism and inflammatory bowel disease.

Trump’s transition team is not commenting on any plans they might have to change federal policy on vaccinations. Trump has previously said that he would push to eliminate …
Relationship of the expression of IL-32 on NF-κB and p-p38 MAP kinase pathways in human esophageal cancer.
Authors: Nasser Ghaly Yousif, Fadhil al-Amran, Hassan Al-khirsani
Journal: Journal of Clinical Oncology (2012)

59 Background: Esophageal cancer is the seventh leading cause of cancer death in males in the United States, and a strong link has been demonstrated between inflammation and esophageal cancer. Interleukin (IL)-32 is a recently described proinflammatory cytokine characterized by the induction of nuclear factor NF-κB activation, the p38 MAPK also plays an important role in key cellular processes related to inflammation and cancer. We investigated whether the IL-32 expression may be involved in esophageal carcinogenesis through modulates the activity of NF-κB and p- p38 MAPK. Methods: Malignant esophageal and blood samples were obtained from 65 operable untreated patients, normal samples was obtained from 35 patients operated for other reasons as control. IL-32 expression, phosphorylated P38MAPK are visualized by immunohistochemistry, RT-PCR for IL-32 mRNA expression and for detected cytokines (TNF-α, IL-1 β, IL-6 and IL-8 ), NF-kB phosphorylation was analyzed by immunoblotting, ELISA for further detection IL-32 and cytokines concentration in the patients sera. Results: IL-32 expression was increased in malignant esophageal samples compared with control (P = 0.01),and mostly in adenocarcinomas type (76.7%) and (21%) in squamous cell carcinomas. IL-32 expression detected at the mRNA level (P = 0.007 vs. control), and its correlated with NF-κB activation (P = 0.003), and up-regulation of phospho p38MAPK (P= 0.004), and also increased in the cytokines concentration compared with the control samples. Conclusions: Understanding the pathway of IL-32 expression to stimulates the secretion cytokines via the activation of NF-κB and up-regulation of p- p38MAPK might be responsible in the esophageal carcinogenesis and used as tumor marker.
Rationale for Therapy Discontinuation in Patients with Lower-Risk Transfusion-Dependent Myelodysplastic Syndromes (MDS)
Authors: Aaron T. Gerds, Shaloo Gupta, Gary Binder, Mikkael A. Sekeres, Aziz Nazha, Hetty E. Carraway, Stephanie Hawthorne, Kristen King-Concialdi, Michael McGuire
Journal: Blood (2016)
Fuhrman grade and concomitant bisphosphonates as additional prognostic factors in metastatic renal cell carcinoma with bone metastases treated with sunitinib.
Authors: B. L. Beuselinck, J. Medioni, P. Wolter, A. Blesius, A. Karadimou, P. Schöffski, B. J. Escudier, J. Zucman-Rossi, R. Paridaens, S. Oudard
Journal: Journal of Clinical Oncology (2011)

388 Background: With a median progression-free survival(PFS) of 8.2 months (mo) (vs. 19.1 mo; p&lt;0.0001) and overall survival (OS) of 19.5 mo (vs. 38.5 mo; p&lt;0.0001), metastatic renal cell carcinoma (m-RCC) patients (pts) with bone metastases (BM) have a poorer outcome under sunitinib (SUN) than pts without BM (Beuselinck et al, Annals of Oncology 2010). The aim of this retrospective study was to determine additional prognostic factors in this poor risk subgroup of pts. Methods: We collected data on classical prognostic factors for m-RCC, Fuhrman grade, number of BM, and bone-oriented therapy in the charts of 80 m-RCC pts with BM who started first-line SUN between 01/2005 and 12/2009 in 4 academic centers in Belgium and France. Univariate analysis was conducted using Maentel Hetzel test. Validation of these findings on a second series of m-RCC patients is ongoing. Multivariate analysis will be performed on the total series. Results: In the total population, median PFS and OS were 9.8 and 20.6 mo. Pts with Fuhrman grade 4 tumors (MSKCC prognosis: intermediate 50%; poor 50%) had a PFS of 4.5 mo vs. 12.3 mo for Fuhrman grade 1-2-3 tumors (MSKCC prognosis: good 20%; intermediate 60%; poor 20%) (p=0.005). OS was 13.5 mo vs. 26.5 mo respectively (p=0.003). There was no difference in PFS and OS between pts with Fuhrman grade 1-2 and Fuhrman grade 3 tumors. The number of BM had no significant influence on PFS and OS. Whether or not radiation therapy and/or surgery had been applied to all BM before starting SUN was a factor without influence on PFS or OS. Concomitant bisphosphonates (BF) and SUN administration was analyzed on all the evaluable pts (24) treated at the University Hospitals Leuven. 14 pts (MSKCC prognosis: poor: 8; intermediate: 6) received concomitant BF. 10 pts (MSKCC prognosis: poor: 5; intermediate: 5) did not. Median PFS was 16.3 and 3.4 mo (p=0.03) and OS 18.1 and 13.9 mo respectively (not significant). Results of the validation series and multivariate analysis will be presented. Conclusions: m-RCC pts combining BM and Fuhrman grade 4 tumors have a very poor outcome on SUN. Concomitant use of BF may be a strategy to improve PFS in pts with bone metastatic RCC. No significant financial relationships to disclose.
Unexpected hyperparathyroidism in metastatic renal cell carcinoma patients treated with sunitinib.
Authors: R. Mazzanti
Journal: Journal of Clinical Oncology (2011)

380 Background: Sunitinib malate is a tyrosine kinase inhibitor, active against tyrosine kinase receptors involved in tumour growth and angiogenesis, and is a potent substrate of p-glycoprotein. This study was conducted to assess whether sunitinib could affect phospho-calcium metabolism. This because both sunitinib and parathyroid hormone have been suggested to be substrates of p-glycoprotein. Here we report the incidence of newly onset hyperparathyroidism in a cohort of patients affected by metastatic renal cell carcinoma (mRCC), treated with sunitinib. Methods: Parathyroid and calcium metabolism function tests were prospectively evaluated in patients receiving a daily 50 mg sunitinib for mRCC according to classic 6-week schedule. Between July 2008 and July 2010, 25 patients received a sunitinib treatment at our institution and resulted eligible for evaluation. Median patients age was 64.3 years old (range 48-79). Parathyroid hormone (PTH), serum and urinary phosphate and calcium, were measured at the beginning of treatment and at the end of each sunitinib ON period. Results: During sunitinib therapy, 17 patients (68%) developed elevated serum parathyroid hormone, with low-to-normal serum calcium and phosphate. On average patients presented an elevation of PTH after 3 sunitinib cycles (range 1-5). Those presenting elevated PTH showed low or undetectable urinary calcium levels. Conclusions: Hyperparathyroidism develops in a high percentage of patients undergoing sunitinib. A similar observation was reported among patients on imatinib, due to an inhibition of PDGF receptor both on osteoclasts and osteoblasts. In these patients, a temporary decrease of serum ionized calcium was supposed as the pathogenetic mechanism of hyperparathyroidism. As sunitinib inhibits PDGF receptors', similar events could be hypothesized. This observation suggests that abnormalities in bone metabolism are a common feature of tyrosine kinases inhibitors targeting PDGF receptors. Routine monitoring of bone metabolism during sunitinib therapy is therefore recommended. No significant financial relationships to disclose.
ATF6 Decreases Myocardial Ischemia/Reperfusion Damage and Links ER Stress and Oxidative Stress Signaling Pathways in the Heart
Authors: Jung-Kang Jin, Erik A. Blackwood, Khalid Azizi, Donna J. Thuerauf, Asal G. Fahem, Christoph Hofmann, Randal J. Kaufman, Shirin Doroudgar, Christopher C. Glembotski
Journal: Circulation Research (2016)

Rationale: Endoplasmic reticulum (ER) stress causes the accumulation of misfolded proteins in the ER, activating the transcription factor, ATF6 (activating transcription factor 6 alpha), which induces ER stress response genes. Myocardial ischemia induces the ER stress response; however, neither the function of this response nor whether it is mediated by ATF6 is known. Objective: Here, we examined the effects of blocking the ATF6-mediated ER stress response on ischemia/reperfusion (I/R) in cardiac myocytes and mouse hearts. Methods and Results: Knockdown of ATF6 in cardiac myocytes subjected to I/R increased reactive oxygen species and necrotic cell death, both of which were mitigated by ATF6 overexpression. Under nonstressed conditions, wild-type and ATF6 knockout mouse hearts were similar. However, compared with wild-type, ATF6 knockout hearts showed increased damage and decreased function after I/R. Mechanistically, gene array analysis showed that ATF6, which is known to induce genes encoding ER proteins that augment ER protein folding, induced numerous oxidative stress response genes not previously known to be ATF6-inducible. Many of the proteins encoded by the ATF6-induced oxidative stress genes identified here reside outside the ER, including catalase, which is known to decrease damaging reactive oxygen species in the heart. Catalase was induced by the canonical ER stressor, tunicamycin, and by I/R in cardiac myocytes from wild-type but not in cardiac myocytes from ATF6 knockout mice. ER stress response elements were identified in the catalase gene and were shown to bind ATF6 in cardiac myocytes, which increased catalase promoter activity. Overexpression of catalase, in vivo, restored ATF6 knockout mouse heart function to wild-type levels in a mouse model of I/R, as did adeno-associated virus 9–mediated ATF6 overexpression. Conclusions: ATF6 serves an important role as a previously unappreciated link between the ER stress and oxidative stress gene programs, supporting a novel mechanism by which ATF6 decreases myocardial I/R damage.
Adaptive-predictive organ localization (a-POLO) in the clinic: Updated results in hypofractionated bladder radiotherapy.
Authors: F. McDonald, S. Lalondrelle, H. Taylor, V. Harris, V. Hansen, V. Khoo, R. A. Huddart
Journal: Journal of Clinical Oncology (2011)

282 Background: The A-POLO strategy allows the optimal 'plan of the day' to be selected online for radiotherapy (RT) delivery. The methodology is implemented in a phase II study of patients with muscle-invasive bladder cancer who are not suitable for cystectomy/daily RT and are receiving hypofractionated RT. Methods: Planning scans were performed at 0 and 30 minutes post void (CT0 and CT30). Three conformal plans were created (small, intermediate, large) ( Table ). Patients were prescribed 6Gy weekly for 5–6 weeks. A pre-RT cone beam CT (CBCT) scan and online set-up correction were performed. The plan giving the optimal target coverage was selected by 2 observers. Offline plan selection was also carried out by an independent observer. A post-RT CBCT was acquired to calculate the percentage of the CTV covered by 95% of the dose (V95). The mean A- POLO volume was compared to our previous institutional standard PTV (1.5cm isotropic margins) (PTViso). Outcome data were collected. Results: A total of 77 RT fractions were delivered to 14 patients. The small plan was delivered for 38 (49%) fractions and the large for 6 (8%) fractions. The concordance rate between online and offline plan selection was 71/77 (92%). The mean CTV V95 was 99% (patient mean range 97–100%). The mean time between the pre- and post-treatment CBCT was 15 minutes. The mean reduction between PTViso and mean A-POLO PTV was 42% (range 16– 59%). 2 patients had grade (G) 3 (CTCv3.0) treatment-related acute toxicity. There have been no treatment-related G4 acute or G3 late toxicities. With a median follow-up of 7.3 months 10 patients are alive with 8 disease free (1 local and 1 distant relapse). Conclusions: Implementation of A-POLO RT is feasible, well tolerated, and associated with good concordance in 'plan of the day' selection. An individualized treatment plan can be delivered with each fraction to achieve a reduction in PTV compared to PTViso with maintenance of target coverage. [Table: see text] No significant financial relationships to disclose.
Survival of Patients with High Risk Hematological Malignancy after Allogeneic Transplant from HLA Identical Siblings Is Comparable to That of Patients Transplanted from Haploidentical, Unmanipulated Bone Marrow Donor: Results of a Matched-Pair Analysis from the Rome Transplant Network
Authors: William Arcese, Raffaella Cerretti, Laura Cudillo, Gottardo De Angelis, Alessandra Picardi, Paolo de Fabritiis, Teresa Dentamaro, Andrea Tendas, Luca Cupelli, Andrea Mengarelli, Francesco Marchesi, Anna Chierichini, Barbara Anaclerico, Maria Cristina Tirindelli, Elisabetta Cerchiara, Enrico Montefusco, Antonella Ferrari, Benedetta Mariotti, Eleonora Ceresoli, Gaspare Adorno, Fabio Di Piazza, Giuseppe Gentile, Loredana Sarmati
Journal: Blood (2014)
Can contemporary targeted therapies provide clinically meaningful changes in renal cell carcinoma venous tumor thrombi?
Authors: S. E. Delacroix, B. F. Chapin, N. Cost, J. A. Karam, S. H. Culp, E. J. Abel, G. Gonzalez, V. Margulis, C. G. Wood
Journal: Journal of Clinical Oncology (2011)

390 Background: Renal cell carcinoma (RCC) tumor thrombus regression has been reported after treatment with contemporary targeted therapies. We sought to identify clinically meaningful changes in tumor thrombi in a series of patients treated with targeted therapies. Methods: A University of Texas M. D. Anderson institutional database was queried for patients treated with targeted therapy while the primary RCC remained in situ. The subset of patients with a vascular tumor thrombus was assessed for radiographic responses of tumor thrombi. Pathology was obtained from a percutaneous biopsy or the surgical specimen. The modified Clavien system was used to grade complications within 12 months of surgery. Clinically meaningful changes were defined as changes in the anatomic thrombus level or changes altering surgical approach. Results: A total of 178 patients were treated with targeted therapy with the primary tumor in situ. Venous tumor thrombus was present in 27% (n=48) and comprised our study cohort. The primary histology was clear cell in 75% of cases and 47/48 patients presented with metastatic disease. Prior to treatment, the tumor thrombus was within the renal vein (RV) in 60% (29/48-Level 0), the first 2 cm of the inferior vena cava in 10% (5/48-Level 1), &gt; 2 cm above the RV in 21% (10/48-Level 2), at the level of the hepatics but below the diaphragm in 6% (3/48-Level 3), and above the diaphragm in 2% (1/48-Level 4). After a median duration of therapy of 2.75 months, clinically meaningful changes occurred in 25% of patients (12/48). Of these, progression occurred in 58% (7/12) while 42% (5/12) had regression of tumor thrombus. Fourteen patients (30%) received surgery after targeted therapy. Clavien categorized complications ≥ grade 3 occurred in 50% of surgical cases. No patient experienced a pulmonary embolism with treatment or during follow up. Conclusions: To our knowledge,this is the largest reported series of RCC patients with an in-situ venous tumor thrombus treated with targeted therapy. Although no patient experienced a pulmonary embolism, the use of targeted therapy with the primary goal of obtaining clinically meaningful reductions in tumor thrombi does not appear to be a promising therapeutic option. No significant financial relationships to disclose.
Post-Transplant Lymphoproliferative Disorders in Transplant Recipients: 14-Yr Experience at the Hospital Israelita Albert Einstein - Brazil
Authors: Danielle Isadora Blumenschein, Juliana Dall Agnol da Rocha, Guilherme Fleury Perini, Iracema Esteves, Alanna Marra P. S. Bezerra, Denise da Cunha Pasqualin, Andreza Alice Feitosa Ribeiro, Fabio Pires de Souza Santos, Nelson Hamerschlak, Ricardo Helman
Journal: Blood (2016)
Differential Expression of P-Glycoprotein, but Not of MRP, LRP and BCRP in Leukemic Stem Cells Compared to More Differentiated CD34+ CD38+ Acute Myeloid Leukemia Blasts.
Authors: Lorena L. Figueiredo-Pontes, Maria C. Pintao, Luciana C. Oliveira de Oliveira, Leandro F. Dalmazzo, Rafael H. Jacomo, Aglair B. Garcia, Roberto P. Falcao, Eduardo M. Rego
Journal: Blood (2006)
Revisiting the prognostic significance of positive peritoneal cytology in pancreatic cancer.
Authors: Kathryn T. Chen, Smit Singla, Pavlos Papavasiliou, Karthik Devarajan, John Parker Hoffman
Journal: Journal of Clinical Oncology (2012)

177 Background: Positive peritoneal cytology (PPC) in the setting of pancreatic cancer predicts a poor prognosis, such that it is considered metastatic disease in the American Joint Commission on Cancer staging guidelines. We re-evaluate the role of PPC, with particular attention to outcomes following neoadjuvant therapy. Methods: We retrospectively identified 185 patients from January 1, 2000 to present with the diagnosis of pancreatic adenocarcinoma who had undergone peritoneal washings with cytology at the time of planned resection. Data regarding demographics, tumor stage, intraoperative cytology, surgical and chemoradiation therapeutics, and clinicopathological outcomes were analyzed, with the primary endpoints being disease-free and overall survival (DFS and OS). Results: 20 patients (11%) had PPC at the time of planned resection; of these, 11 patients (55%) received neoadjuvant therapy prior to surgery. 165 patients (89%) had negative peritoneal cytology (NPC) at the time of planned resection; of these, 75 (45%) received neoadjuvant therapy prior to surgery. All patients proceeded with resection in the absence of visible metastatic disease. 42% of NPC reached 2-year survival compared to just 20% of patients with PPC. Overall, patients with PPC vs. NPC had significantly poorer DFS (p&lt;0.0064) and OS (p&lt;0.0135). When stratifying by neoadjuvant therapy, in those patients with stage II disease or higher who did not receive neoadjuvant therapy, multivariable CART analysis revealed that PPC predicted poorer DFS compared with NPC (p&lt;0.004). However, among stage II or higher disease receiving neoadjuvant therapy, it failed to show a significant difference in DFS or OS between PPC and NPC. Conclusions: Overall, patients with positive peritoneal cytology are shown to have worse DFS and OS compared to patients with negative peritoneal cytology in pancreatic adenocarcinoma. However, after multivariable analysis, the prognostic significance of positive peritoneal cytology disappears in those patients with stage II and higher disease receiving neoadjuvant therapy.