Dynamics of EGFR Mutation Load in Plasma for Prediction of Treatment Response and Disease Progression in Patients With EGFR-Mutant Lung Adenocarcinoma

Background

The assessment of epidermal growth factor receptor (EGFR) mutations is crucial for the management of patients with lung adenocarcinoma. Circulating tumor DNA (ctDNA)-based assessment offers advantages over tumor as a minimally invasive method able to capture tumor heterogeneity.

Understanding the supportive care needs of Hispanic men cancer survivors

Objective. To date, there is a paucity of research and information on Hispanic men cancer survivors (HMCS), who comprise part of the largest and fastest growing racial/ethnic minority group in the country. The purpose of this paper is to provide a deeper understanding of the supportive care needs of HMCS.

Design. Three focus groups with a community sample of HMCS (n?=?18) and interviews with providers (n?=?5) were conducted to explore the supportive care needs of Hispanic men who had been diagnosed with cancer within the last five years. The data were analyzed using applied thematic analysis techniques.

Results. Findings from focus groups and interviews are presented concurrently. The overarching themes that emerged were the need for: culturally sensitive cancer care and better communication with providers; cancer treatment-related information and comprehensive survivorship care; support and to connect with other cancer survivors and the need to negotiate changing gender role expectations and still provide for their family.

Conclusion. Study findings contribute to the literature by presenting the supportive care needs of HMCS and illustrate the need for continued research to address disparities in access to cancer information and in the provision of culturally sensitive care. We provide recommendations and suggestions to address the supportive care needs of HMCS.     

Diabetic gastroenteropathy: An underdiagnosed complication

This article is an extensive review that provides an update on the pathophysiology, symptoms, diagnosis, and treatment of diabetic gastroenteropathy. There is no reported prevalence, but it has been described that patients with type 1 diabetes have a cumulative incidence at 10 years of 5.2%, and type 2 patients, 1%. Also, in the group of type 1 diabetes, it has been observed that women are more likely to present this condition (5.8% vs 3.5%). Many factors are associate with its development (e.g., hyperglycemia, vagal dysfunction, loss of expression of neural nitric oxide synthase in the myenteric plexus, alterations in the Cajal interstitial cell network, and oxidative stress). Gastrointestinal discomfort could be perceived 70% higher in diabetic patients, describing that 25% of diabetic patients experience gastrointestinal symptoms. Diabetic enteropathy could affect any portion of the gastrointestinal tract, but esophageal alterations were described in more than 60% of diabetic patients, also 60% of them present constipation, and 20%, diarrhea. Gastric emptying scintigraphy is useful to evaluate gastroparesis, therefore, gastric retention of more than 60% at 2 h has a sensitivity of 100% and specificity of 20% for diagnosis; however, other studies such as breath tests, with a sensitivity of 89% and a specificity of 80%, or the endoscopic capsule contribute to the diagnosis. There is no cure; however, management must be multidisciplinary, focused on slowing the progression of diabetic gastroenteropathy, reducing symptoms, and restoring function; that includes nutritional recommendation, maintain glucose levels kept below 180 mg/dL, use of prokinetics, anti-emetics; nowadays, it has been special interest in surgical treatment, such as pyloroplasty, also gastric electrical stimulation appears to be another alternative.     

Prevalence,prenatal diagnosis and clinical features of oculo-auriculo-vertebral spectrum: a registry-based study in Europe

Oculo-auriculo-vertebral spectrum is a complex developmental disorder characterised mainly by anomalies of the ear, hemifacial microsomia, epibulbar dermoids and vertebral anomalies. The aetiology is largely unknown, and the epidemiological data are limited and inconsistent. We present the largest population-based epidemiological study to date, using data provided by the large network of congenital anomalies registries in Europe. The study population included infants diagnosed with oculo-auriculo-vertebral spectrum during the 1990–2009 period from 34 registries active in 16 European countries. Of the 355 infants diagnosed with oculo-auriculo-vertebral spectrum, there were 95.8% (340/355) live born, 0.8% (3/355) fetal deaths, 3.4% (12/355) terminations of pregnancy for fetal anomaly and 1.5% (5/340) neonatal deaths. In 18.9%, there was prenatal detection of anomaly/anomalies associated with oculo-auriculo-vertebral spectrum, 69.7% were diagnosed at birth, 3.9% in the first week of life and 6.1% within 1 year of life. Microtia (88.8%), hemifacial microsomia (49.0%) and ear tags (44.4%) were the most frequent anomalies, followed by atresia/stenosis of external auditory canal (25.1%), diverse vertebral (24.3%) and eye (24.3%) anomalies. There was a high rate (69.5%) of associated anomalies of other organs/systems. The most common were congenital heart defects present in 27.8% of patients. The prevalence of oculo-auriculo-vertebral spectrum, defined as microtia/ear anomalies and at least one major characteristic anomaly, was 3.8 per 100 000 births. Twinning, assisted reproductive techniques and maternal pre-pregnancy diabetes were confirmed as risk factors. The high rate of different associated anomalies points to the need of performing an early ultrasound screening in all infants born with this disorder.     

Targeting oncogenic ALK: a promising strategy for cancer treatment

Recently, the anaplastic lymphoma kinase (ALK) has been found to be altered in several solid and hematologic tumors. Novel drugs targeting this tyrosine kinase receptor are under development, and early clinical trials are showing promising activity in non-small cell lung cancer patients with ALK+ tumors. Here, we review the structure and function of the ALK receptor, the mechanisms associated with its deregulation in cancer, methods for ALK detection in tumor samples, its potential as a new marker for candidate patient selection for tailored therapy, and novel drugs under development that target ALK.     

Behavioral coping strategies in response to social stress are associated with distinct neuroendocrine, monoaminergic and immune response profiles in mice

Individual variation in behavioral coping strategies to stress implies that animals may have a distinct physiological adaptation to stress; these differences may underlie differences in vulnerability to stress-related diseases. This study was designed to test the hypothesis that different behavioral coping strategies (active vs. passive) are stable over time and that they would be associated with differences in hypothalamic-pituitary-adrenal (HPA) and sympathetic-adreno-medular (SAM) axes, and monoaminergic and immune activity. Male mice were subjected to social stress. Twelve days after the first social interaction, mice were subjected to a second identical social stress interaction. Behavior was videotaped and assessed during both sessions. One hour after the final social interaction, serum was collected for corticosterone and adrenaline concentrations and brains were collected for hypothalamic corticotrophin-releasing hormone (CRH) mRNA expression. Monoaminergic system activity was determined by mRNA expression of serotonin, dopamine and noradrenaline synthetic enzymes in the brain stem. Immune system activity was determined by mRNA expression of hypothalamic interleukin-1β (IL-1β) and splenic IL-1β and interleukin-2 (IL-2). Mice engaging in a passive strategy had higher serum corticosterone and lower serum adrenaline concentrations than the active group. The passive group showed lower hypothalamic mRNA expression of IL-1β and CRH and lower splenic mRNA expression of IL-2 and IL-1β relative to mice in the active group. An active strategy was associated with higher expression of the dopaminergic synthetic enzyme, while a passive strategy was associated with decreased expression of the serotonergic synthetic enzyme. These findings indicate that individual coping strategies are stable over time and are related to differences in the physiological stress response and immune activity.     

MET phosphorylation predicts poor outcome in small cell lung carcinoma and its inhibition blocks HGF-induced effects in MET mutant cell lines

Background:

Small cell lung carcinoma (SCLC) has poor prognosis and remains orphan from targeted therapy. MET is activated in several tumour types and may be a promising therapeutic target.

Methods:

To evaluate the role of MET in SCLC, MET gene status and protein expression were evaluated in a panel of SCLC cell lines. The MET inhibitor PHA-665752 was used to study effects of pathway inhibition in basal and hepatocyte growth factor (HGF)-stimulated conditions. Immunohistochemistry for MET and p-MET was performed in human SCLC samples and association with outcome was assessed.

Results:

In MET mutant SCLC cells, HGF induced MET phosphorylation, increased proliferation, invasiveness and clonogenic growth. PHA-665752 blocked MET phosphorylation and counteracted HGF-induced effects. In clinical samples, total MET and p-MET overexpression were detected in 54% and 43% SCLC tumours (n=77), respectively. MET phosphorylation was associated with poor median overall survival (132 days) vs p-MET negative cases (287 days)(P<0.001). Phospho-MET retained its prognostic value in a multivariate analysis.

Conclusions:

MET activation resulted in a more aggressive phenotype in MET mutant SCLC cells and its inhibition by PHA-665752 reversed this phenotype. In patients with SCLC, MET activation was associated with worse prognosis, suggesting a role in the adverse clinical behaviour in this disease.