High expression of suppressor of cytokine signaling-2 predicts poor outcome in pediatric acute myeloid leukemia: a report from the Children's Oncology Group.

Deregulated cytokine signaling is a characteristic feature of acute myeloid leukemia (AML), and expression signatures of cytokines and chemokines have been identified as a significant prognostic factor in this disease. Given this aberrant signaling, we hypothesized that expression of suppressor of cytokine signaling-2 (SOCS2), a negative regulator of cytokine signaling, might be altered in AML and could provide predictive information. Among 188 participants of the Children's Oncology Group AAML03P1 trial, SOCS2 mRNA levels varied > 6000-fold.

Patterns of latrine use by raccoons (Procyon lotor) and implication for Baylisascaris procyonis transmission.

Mammals often use latrine sites for defecation, yet little is known about patterns of latrine use in many common species such as raccoons (Procyon lotor). Because raccoon latrines are important foci for the transmission of raccoon roundworm (Baylisascaris procyonis), documenting metrics of raccoon latrine use may have public health implications. Although some studies have provided evidence that multiple raccoons visit single latrine sites, exact latrine visitation patterns of raccoons have never been documented.

ICP, BMI, surgical repair, and CSF diversion in patients presenting with spontaneous CSF otorrhea.

Objective: To assess intracranial pressure (ICP), body mass index (BMI), surgical repair, and cerebrospinal fluid (CSF) diversion in patients presenting with spontaneous CSF otorrhea.

Study Design: Retrospective series review.

Setting: Tertiary referral center.

Treatment outcomes in patients treated with CyberKnife radiosurgery for vestibular schwannoma.

Objective: To evaluate tumor control, hearing, tinnitus, and balance outcomes of patients treated with CyberKnife (CK) radiosurgery for vestibular schwannoma (VS).

Study Design: Retrospective series review.

Setting: Tertiary referral center.

Comparative effectiveness research: moving medical oncology forward.

Comparative effectiveness research (CER) is critically needed in medical oncology to improve the care being delivered to oncology patients. As medical oncologists are forced to rely on insufficient data as a part of daily treatment decision making, and as the cancer treatment landscape evolves quickly relative to other areas of medicine, CER is particularly pressing in our field. Continued reliance on randomized clinical trials is a part of the solution, but it cannot be the sole answer.

Real-world outcomes in metastatic renal cell carcinoma: insights from a Joint Community-Academic Registry.

Introduction: As new therapeutics for metastatic renal cell carcinoma (mRCC) are quickly introduced to market, comparative randomized trial evidence guiding treatment decisions is lacking, especially in the second treatment exposure and beyond. As a demonstration case, we studied mRCC in real-world clinical settings by creating a joint community-academic retrospective mRCC registry to assess outcomes.

Materials And Methods: For this overall survival (OS) analysis, the analytic cohort included all patients in the registry diagnosed between January 1, 2007, to May 31, 2011 (N = 384).

Haematopoietic cell transplantation for acute leukaemia and advanced myelodysplastic syndrome in Fanconi anaemia.

Acute leukaemia or advanced myelodysplastic syndrome (MDS ≥ 5% blasts) in Fanconi anaemia (FA) patients is associated with a poor prognosis. We report 21 FA patients with acute leukaemia or advanced MDS who underwent haematopoietic cell transplantation (HCT) at the University of Minnesota between 1988 and 2011. Six patients had biallelic BRCA2 mutations.

Will biosimilars gain momentum?

Biosimilars, also known as follow-on biologics, continue to be an area of great interest in oncology because of the potential cost savings and improved access related to their use, yet significant confusion remains regarding their introduction in the United States. The regulatory and legal hurdles remain poorly defined, and companies producing branded products have been battling their introduction. The European Union provided a pathway for approval in 2004, with various agents reaching the market since that time.

Abundant in vitro expression of the oncofetal ED-B-containing fibronectin translates into selective pharmacodelivery of (131)I-L19SIP in a prostate cancer patient.

Purpose: The extradomain B of fibronectin (ED-B) is a promising vascular target for selective pharmacodelivery in cancer patients. We analyzed a large series of prostatectomies from patients with prostate cancer, hyperplastic prostate disease, and normal prostates to study extent and tumor-selectivity of ED-B expression.

Methods: Using immunohistology, 68 adenocarcinomas of the prostate or prostate cancer-inflicted lymph nodes, 4 samples of benign prostatic hyperplasia, and 6 normal prostate glands were studied for ED-B expressing newly formed blood vessels.

Raccoon social networks and the potential for disease transmission.

Raccoons are an important vector of rabies and other pathogens. The degree to which these pathogens can spread through a raccoon population should be closely linked to association rates between individual raccoons. Most studies of raccoon sociality have found patterns consistent with low levels of social connectivity within populations, thus the likelihood of direct pathogen transmission between raccoons is theoretically low.

BIRC5 (survivin) splice variant expression correlates with refractory disease and poor outcome in pediatric acute myeloid leukemia: a report from the Children's Oncology Group.

Background: The inhibitor-of-apoptosis protein survivin, encoded by BIRC5, regulates apoptosis, cell division and proliferation. Several survivin splice variants have been described however, the prognostic significance of their expression has not been well defined in pediatric acute myeloid leukemia (AML).

Procedure: Quantitative expression analyses of BIRC5 mRNA (n = 306) and survivin transcript splice variants (n = 90) were performed on diagnostic bone marrow samples from children with de novo AML treated on the clinical trials CCG-2961 and AAML03P1, then correlated with disease characteristics and clinical outcome.

Rinne revisited: steel versus aluminum tuning forks.

Objective: (1) Determine whether tuning fork material (aluminum vs stainless steel) affects Rinne testing in the clinical assessment of conductive hearing loss (CHL). (2) Determine the relative acoustic and mechanical outputs of 512-Hz tuning forks made of aluminum and stainless steel.

Study Design: Prospective, observational.

Outcome of pediatric patients with acute myeloid leukemia (AML) and -5/5q- abnormalities from five pediatric AML treatment protocols: a report from the Children's Oncology Group.

Background: Abnormalities of chromosome 5q (-5/5q-) are associated with poor prognosis in adults with acute myeloid leukemia (AML). However, there are no large studies on outcomes of children with -5/5q- AML. To determine the disease correlates of this group, we retrospectively analyzed cytogenetic data from five studies of childhood AML.

Exogenous hormone use, reproductive history and risk of adult myeloid leukaemia.

Background: A hormonal aetiology is one explanation for the lower incidence of myeloid leukaemia in women compared with men.

Methods: In this population-based case-control study, we evaluated associations between exogenous hormone use and reproductive history and myeloid leukaemia, overall and by disease subtype.

Results: We observed a suggestive association between oral contraceptive use and acute myeloid leukaemia (odds ratio=0.

The prognostic effect of high diagnostic WT1 gene expression in pediatric AML depends on WT1 SNP rs16754 status: report from the Children's Oncology Group.

Background: WT1 is aberrantly over-expressed in most cases of AML. We recently demonstrated that WT1 SNP rs16754 correlates with favorable outcome and high diagnostic WT1 expression in childhood AML. We examined the clinical correlates of diagnostic WT1 expression within a contemporary COG trial and determined whether its prognostic impact differs between SNP+ and SNP- patients.

Three-dimensional kinematic stress magnetic resonance image analysis shows promise for detecting altered anatomical relationships of tissues in the cervical spine associated with painful radiculopathy.

For some patients with radiculopathy a source of nerve root compression cannot be identified despite positive electromyography (EMG) evidence. This discrepancy hampers the effective clinical management for these individuals. Although it has been well-established that tissues in the cervical spine move in a three-dimensional (3D) manner, the 3D motions of the neural elements and their relationship to the bones surrounding them are largely unknown even for asymptomatic normal subjects.

High EVI1 expression is associated with MLL rearrangements and predicts decreased survival in paediatric acute myeloid leukaemia: a report from the children's oncology group.

Ectopic viral integration site-1 (EVI1) is highly expressed in certain cytogenetic subsets of adult acute myeloid leukaemia (AML), and has been associated with inferior survival. We sought to examine the clinical and biological associations of EVI1(high) , defined as expression in excess of normal controls, in paediatric AML. EVI1 mRNA expression was measured via quantitative real-time polymerase chain reaction in diagnostic specimens obtained from 206 patients.

Succinyl-CoA:3-sulfinopropionate CoA-transferase from Variovorax paradoxus strain TBEA6, a novel member of the class III coenzyme A (CoA)-transferase family.

The act gene of Variovorax paradoxus TBEA6 encodes a succinyl-CoA:3-sulfinopropionate coenzyme A (CoA)-transferase, Act(TBEA6) (2.8.3.

The ethics of health information technology in oncology: emerging isssues from both local and global perspectives.

Health information technology (HIT) is ever-increasing in complexity and has incrementally become a fundamental part of our everyday clinical lives. As HIT becomes more complex and commonplace, so do the questions it raises about stewardship and usage of data, along with the ethics of these applications. With the development of rapid-learning systems, such as ASCO's CancerLinQ, careful thought about the ethics and applications of these technologies is necessary.

The economics of new drugs: can we afford to make progress in a common disease?

The concept of personalized medicine is beginning to come to fruition, but the cost of drug development is untenable today. To identify new initiatives that would support a more sustainable business model, the economics of drug development are analyzed, including the cost of drug development, cost of capital, target market size, returns to innovators at the product and firm levels, and, finally, product pricing. We argue that a quick fix is not available.

Characteristics of oncology clinical trials: insights from a systematic analysis of ClinicalTrials.gov.

Importance: Clinical trials are essential to cancer care, and data about the current state of research in oncology are needed to develop benchmarks and set the stage for improvement.

Objective: To perform a comprehensive analysis of the national oncology clinical research portfolio.

Design: All interventional clinical studies registered on ClinicalTrials.

Significance of expression of ITGA5 and its splice variants in acute myeloid leukemia: a report from the Children's Oncology Group.

Acute myeloid leukemia (AML) encompasses a heterogeneous group of diseases, and novel biomarkers for risk refinement and stratification are needed to optimize patient care. To identify novel risk factors, we performed transcriptome sequencing on 68 diagnostic AML samples and identified 2 transcript variants (-E2 and -E2/3) of the α-subunit (ITGA5) of the very late antigen-5 integrin. We then quantified expression of ITGA5 and these splice variants in specimens from participants of the AAML03P1 trial.

Gain of interaction with IRS1 by p110α-helical domain mutants is crucial for their oncogenic functions.

PIK3CA, which encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase α, is frequently mutated in human cancers. Most of these mutations occur at two hot-spots: E545K and H1047R located in the helical domain and the kinase domain, respectively. Here, we report that p110α E545K, but not p110α H1047R, gains the ability to associate with IRS1 independent of the p85 regulatory subunit, thereby rewiring this oncogenic signaling pathway.