Citations

The Mattis Dementia Rating Scale (MDRS) is a multidimensional cognitive measure popular with clinicians for its brevity, diagnostic validity, and utility in monitoring impairment severity. In spite of the test’s significant value, one task can cause discomfort because the patient is asked to name items the examiner is wearing. This task also creates possible cultural bias and standardization issues. We studied 102 MDRS profiles that included this item. Adjusted scores were calculated by giving all patients full credit for the apparel-naming item. The average adjustment was just one point, and the resulting dementia-severity ratings remained unchanged in 97% of the patients. These results show that administration of the item can be defensibly skipped if there is concern about its appropriateness with an individual patient. The adjusted scores provide a viable and fair alternative that preserves the psychometric properties of this useful instrument.

BACKGROUNDThe management of pediatric melanoma (PM) has largely been extrapolated from adult data. However, the behavior of PM appears to differ from its adult counterparts. Therefore, an international PM registry was created and analyzed.METHODSTwelve institutions contributed deidentified clinicopathologic and outcome data for patients diagnosed with PM from 1953 through 2008.RESULTSOverall survival (OS) data were reported for 365 patients with invasive PM who had adequate follow‐up data. The mean age of the patients was 16 years (range 1 year‐21 years). The 10‐year OS rate, 80.6%, tended to vary by patient age: 100% for those aged birth to 10 years, 69.7% for those aged > 10 years to 15 years, and 79.5% for those aged > 15 years to 20 years (P = .147). Patients with melanomas measuring ≤ 1 mm had a favorable prognosis (10‐year OS rate of 97%), whereas survival was lower but similar for patients with melanomas measuring > 1 mm to 2 mm, > 2 mm to 4 mm, and > 4 mm (70%, 78%, and 80%, respectively; P = .0077). Ulceration and lymph node metastasis were found to be correlated with worse survival (P = .022 and P = .017, respectively). The 10‐year OS rate was 94.1% for patients with American Joint Committee on Cancer stage I disease, 79.6% for those with stage II disease, and 77.1% for patients with stage III disease (P < .001).CONCLUSIONSTumor thickness, ulceration, lymph node status, and stage were found to be significant predictors of survival in patients with PM, similar to adult melanoma. There is a trend toward increased survival in children aged ≤ 10 years versus adolescents aged > 10 years. Further analyses are needed to probe for potential biological and behavioral differences in pediatric versus adult melanoma. Cancer 2013;119:4012–4019. © 2013 American Cancer Society.

Key PointsPhenotypic and genotypic profiling of MDM2 in DLBCL. MDM2 as a negative regulator of p53 tumor suppressor function.

AbstractRunx2 is the master transcription factor for bone formation. Haploinsufficiency of RUNX2 is the genetic cause of cleidocranial dysplasia (CCD) that is characterized by hypoplastic clavicles and open fontanels. In this study, we found that Pin1, peptidyl prolyl cis–trans isomerase, is a critical regulator of Runx2 in vivo and in vitro. Pin1 mutant mice developed CCD‐like phenotypes with hypoplastic clavicles and open fontanels as found in the Runx2+/− mice. In addition Runx2 protein level was significantly reduced in Pin1 mutant mice. Moreover Pin1 directly interacts with the Runx2 protein in a phosphorylation‐dependent manner and subsequently stabilizes Runx2 protein. In the absence of Pin1, Runx2 is rapidly degraded by the ubiquitin‐dependent protein degradation pathway. However, Pin1 overexpression strongly attenuated uniquitin‐dependent Runx2 degradation. Collectively conformational change of Runx2 by Pin1 is essential for its protein stability and possibly enhances the level of active Runx2 in vivo. J. Cell. Physiol. 228: 2377–2385, 2013. © 2013 Wiley Periodicals, Inc.

AbstractCancer is a multifaceted disease that involves acquisition of genetic mutations, deletions, and amplifications as well as deregulation of epigenetic mechanisms that fine‐tune gene regulation. Key epigenetic mechanisms that include histone modifications, DNA methylation, and non‐coding RNA‐mediated gene silencing are often deregulated in a variety of cancers. Subnuclear localization of key proteins in the interphase nucleus and bookmarking of genes by lineage commitment factors in mitosis—a new dimension to epigenetic control of fundamental biological processes—is also modified in cancer. In this review, we discuss the various aspects of epigenetic control that are operative in a variety of cancers and their potential for risk assessment, early detection, targeted therapy, and personalized medicine. J. Cell. Physiol. 228: 2103–2108, 2013. © 2013 Wiley Periodicals, Inc.

Objectives To investigate the incidence of carcinoma in situ ( CIS ) in Australia and examine implications for its diagnosis and management, as CIS of the urinary bladder is a non‐reportable disease in Australia. Methods Analysis of annual hospitalisation data using A ustralian I nstitute of H ealth and W elfare ( AIHW ) datasets showed an increase in CIS from 2001 onwards. To determine whether the increase seen with AIHW data represented a true increase in the rates offices, patient level data was examined using the Centre for Health record linkage ( CHeReL ) datasets. Results CHeReL linked data of 13 790 males and 5902 females, calculated the average incidence of CIS to be 20.9 per 100 000 and 6.5 per 100 000 respectively in those aged > 50 years, showing a rapid increase in the rates of CIS from 2001. There was an 11% ( P = 0.04) and 14% ( P = 0.02) annual increase in incidence of CIS in men and women and these rates increased with age. Conclusions National data ( AIHW ) substantially underestimate the incidence of CIS in the Australian population. Patient level data suggest CIS rates are rapidly increasing in Australia despite high treatment rates. Closer surveillance and awareness of these high rates warrants further study and we recommend that CIS be considered a reportable disease.

Abstract New approaches to drug development are critically needed to lessen the time, cost, and resources necessary to identify and optimize active agents. Strategies to accelerate drug development include testing drugs earlier in the disease process, such as the neoadjuvant setting. The U.S. Food and Drug Administration (FDA) has issued guidance designed to accelerate drug approval through the use of neoadjuvant studies in which the surrogate short-term endpoint, pathologic response, can be used to identify active agents and shorten the time to approval of both efficacious drugs and biomarkers identifying patients most likely to respond. However, this approach has unique challenges. In particular, issues of patient safety are paramount, given the exposure of potentially curable patients to investigational agents with limited safety experience. Key components to safe drug development in the neoadjuvant setting include defining a study population at sufficiently poor prognosis with standard therapy to justify exposure to investigational agents, defining the extent and adequacy of safety data from phase I, detecting potentially harmful interactions between investigational and standard therapies, improving study designs, such as adaptive strategies, that limit patient exposure to ineffective agents, and intensifying safety monitoring in the course of the trial. The I-SPY2 trial is an example of a phase II neoadjuvant trial of novel agents for breast cancer in which these issues have been addressed, both in the design and conduct of the trial. These adaptations of phase II design enable acceleration of drug development by reducing time and cost to screen novel therapies for activity without compromising safety. Clin Cancer Res; 19(11); 2817–23. ©2013 AACR.