Proteomic profiling of patient-derived glioblastoma xenografts identifies a subset with activated EGFR: implications for drug development

The development of drugs to inhibit glioblastoma (GBM) growth requires reliable preclinical models. To date, proteomic level validation of widely used patient-derived glioblastoma xenografts (PDGX) has not been performed. In the present study, we characterized 20 PDGX models according to subtype classification based on The Cancer Genome Atlas (TCGA) criteria, TP53, PTEN, IDH 1/2 and TERT promoter genetic analysis, EGFR amplification status, and examined their proteomic profiles against those of their parent tumors. The 20 PDGXs belonged to three of four TCGA subtypes: 8 classical, 8 mesenchymal, and 4 proneural; none neural. Amplification of EGFR gene was observed in 9 out of 20 xenografts, and of these, 3 harbored the EGFRvIII mutation. We then performed proteomic profiling of PDGX, analyzing expression/activity of several proteins including EGFR. Levels of EGFR phosphorylated at Y1068 vary considerably between PDGX samples, and this pattern was also seen in primary GBM. Partitioning of 20 PDGX into high (n=5) and low (n=15) groups identified a panel of proteins associated with high EGFR activity. Thus, PDGX with high EGFR activity represent an excellent preclinical model to develop therapies for a subset of GBM patients whose tumors are characterized by high EGFR activity. Further, the proteins found to be associated with high EGFR activity can be monitored to assess the effectiveness of targeting EGFR

Living with itch a patient's guide

Chronic itch can interfere with a person's ability to function, and can even affect quality of life. The authors explain the cascade of physiological events that causes us to experience itch. They describe the many skin diseases and conditions that cause itch, and provide information on preventing, treating, and coping with your condition

A Practical Approach to Diagnosing and Managing Chronic Spontaneous Urticaria

Chronic spontaneous urticaria (CSU) is an unpredictable inflammatory skin condition characterized by the spontaneous onset of itchy wheals, angioedema, or both, which occurs for longer than 6 weeks overall. Despite the relatively straightforward diagnostic algorithm for CSU, relying primarily on a detailed medical history and only limited laboratory tests, patients often wait years to be diagnosed, with many cycling through different healthcare practitioners before a diagnosis is made. Even then, current treatment options for CSU are limited, with approximately half of patients resistant to standard-of-care second-generation antihistamines at standard or higher doses. As such, there is an unmet need for improved, streamlined management for patients with CSU. Here, we review the evidence-based diagnostic algorithm for CSU, consider the required steps of the diagnostic workup, and provide practical, real-world advice on the management of CSU to improve the timely diagnosis and care of patients with this debilitating disease

Breaking the cycle of hair breakage: pearls for the management of acquired trichorrhexis nodosa

Acquired trichorrhexis nodosa (TN) is a common cause of hair loss for patients of all ethnicities. It is especially prevalent in black patients with tightly curled hair types and can present unique diagnostic and therapeutic challenges due to structural differences in these hair types and the combination of various hair care and styling practices that contribute to hair damage. While scalp biopsies can help rule out other etiologies of hair loss, there is a paucity of histologic findings in acquired TN, making this primarily a clinical diagnosis. Instead of more traditional prescription based therapies, the management of this form of hair loss emphasizes protecting the hair shaft and minimizing further damage through the development of a healthy hair care regimen. This involves appropriate selection and use of cleansing products and conditioning agents that help protect the hair from the insults of daily grooming. This paper will review the current literature on acquired TN and will provide guidelines and recommendations for management by reviewing the different types of cleansing and conditioning products that can be used to prevent and/or halt the progression of hair breakage

Diagnostic Workup and Evaluation of Patients with Prurigo Nodularis

Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized oftentimes by symmetrically distributed, severely pruritic nodules. Currently, the pathophysiology of PN remains to be fully elucidated, but emerging evidence suggests that neuroimmune alterations play principal roles in the pathogenesis of PN. There are several associated etiologic factors thought to be associated with PN, including dermatoses, systemic, infectious, psychiatric, and neurologic conditions. We conducted a systematic literature review to evaluate the clinical presentation, diagnosis, and etiologic factors of PN. In this review, we discuss common differential diagnoses of PN and recommend an evidence-based, standardized diagnostic evaluation for those with suspected PN