Improving quality of life in patients with pancreatic neuroendocrine tumor following peptide receptor radionuclide therapy assessed by EORTC QLQ-C30

Introduction

Neuroendocrine tumors (NETs) have proven to be appropriate neoplasms for peptide receptor radionuclide therapy (PRRT), as the majority of these slow-growing malignancies overexpress somatostatin receptors. The aim of this study was to evaluate changes in quality of life (QoL) of patients with P-NET following PRRT.

Methods

Sixty-eight patients with P-NET (31 female, mean age 61.4 y) underwent PRRT: 12 with NET of grade 1, 40 of grade 2, 8 of grade 3 (grade non-available n = 8). Prior to treatment, 39 patients showed ECOG 0, 26 patients ECOG 1, and three patients ECOG 2. Clinical assessment included evaluation of QoL and symptom changes using a standardized questionnaire (EORTC QLQ-C30) and was performed at baseline and every three months following each therapy cycle up to 12 months. Primary analysis compared QoL at baseline and after the fourth treatment cycle (N = 53).

Results

Up to four treatment cycles PRRT were performed for each patient. The median cumulative administered activity was 28.2 GBq. Primary analysis revealed that compared to baseline QoL was significantly improved revealing increased global health status (p = 0.008) and social functioning (p = 0.049) at the end of the study. Furthermore, fatigue and appetite loss showed a significant improvement after the last PRRT cycle (fatigue: p = 0.029, appetite loss p = 0.015). Sub-analyses showed that QoL was improved revealing increased global health status (3 months after first, second, and third treatment cycle p = 0.048, p = 0.002, and p < 0.001, respectively), emotional functioning (3 months after first-third cycle p = 0.003, p = 0.049, and p = 0.001, respectively) and social functioning (3 months after the first and second p < 0.001, and after the third cycle p = 0.015, respectively). Furthermore, some symptoms were significantly alleviated compared with baseline: fatigue (after first-third cycle p = 0.026, p = 0.050, and p = 0.008, respectively), nausea and vomiting (after first and second cycle p = 0.006 and p = 0.001, respectively), dyspnea (after third cycle p = 0.025), appetite loss (after first-third cycle p = 0.010, p = 0.001, and p = 0.009, respectively), constipation (after first-third cycle p = 0.050, p = 0.003, and p = 0.060, respectively).

Conclusion

PRRT is an effective treatment of P-NET improving QoL of patients in terms of increasing global health and mitigation of physical complaints.

     

Prostate-specific membrane antigen in breast cancer: a comprehensive evaluation of expression and a case report of radionuclide therapy

Purpose

Prostate-specific membrane antigen (PSMA), a protein product of the folate hydrolase 1 (FOLH1) gene, is gaining increasing acceptance as a target for positron emission tomography/computer tomography (PET/CT) imaging in patients with several cancer types, including breast cancer. So far, PSMA expression in breast cancer endothelia has not been sufficiently characterized.

Methods

This study comprised 315 cases of invasive carcinoma of no special type (NST) and lobular breast cancer (median follow-up time 9.0 years). PSMA expression on tumor endothelia was detected by immunohistochemistry. Further, vascular mRNA expression of the FOLH1 gene (PSMA) was investigated in a cohort of patients with invasive breast cancer provided by The Cancer Genome Atlas (TCGA).

Results

Sixty percent of breast cancer cases exhibited PSMA-positive endothelia with higher expression rates in tumors of higher grade, NST subtype with Her2-positivity, and lack of hormone receptors. These findings were confirmed on mRNA expression levels. The highest PSMA rates were observed in triple-negative carcinomas (4.5 × higher than in other tumors). Further, a case of a patient with metastatic breast cancer showing PSMA expression in PET/CT imaging and undergoing PSMA radionuclide therapy is discussed in detail.

Conclusions

This study provides a rationale for the further development of PSMA-targeted imaging in breast cancer, especially in triple-negative tumors.

     

Effectiveness of the video-based education in the retention of addiction treatment

Background: In recent years, a range of innovative interventions for drug abuse treatment has been developed. The aim of the present study was to evaluate the effectiveness of video-based education on prevention of relapse and to investigate the factors that play important roles.

Methods: This is a before–after interventional design which was carried out on 40 addict clients who were admitted in the three addiction clinics in the city of Bojnourd, North East of Iran. All participants completed the questionnaire before watching the educational package digital video/versatile disc (DVD)1 and booklet1 as a pretest and one month after watching the DVD2 and reading booklet2 as a post test. The questionnaire contained 25 questions covering five factors, including family’s roles, items, treats, attitude toward behavior, friend’s roles, and self-efficacy. The Statistical Package for the Social Sciences (SPSS)-16 software was applied for data analysis

Results: The results showed that 73% of clients have remained without a history of drug intake during treatment. Family roles (U = 62.5, p = 0.011) and self-efficacy (U = 63.5, p = 0.013) were significant determinant factors for the effectiveness of the addiction treatment program. Conclusion: This study emphasized the effectiveness of the video-based education in retention of addiction treatment. It showed that the video-based education was an effective tool to increase family roles and self-efficacy in the clients.     

Preparation and in vitro/pharmacokinetic/pharmacodynamic evaluation of a slow-release nano-liposomal form of prednisolone

A nano-liposomal carrier was prepared for the anti-inflammatory drug prednisolone acetate (PA). The drug showed remarkable loading in the nano-carriers. The drug-loaded nano-liposmes with average sizes of about 186?nm and zeta potentials of??20?mV were obtained. Our drug release studies showed an apparently zero-order trend with only 18% of the drug released in the first 120 h. Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) analyses showed no chemical interaction between the drug and carrier. Transmission electron microscopy (TEM) imaging showed near-spherical drug-containing nano-carriers. The intramuscular (IM) trial of the nanoformulation compared with the free drug showed both pharmacokinetic (lower C_max, higher area under the curve (AUC)) and pharmacodynamic (higher and longer lasting anti-inflammatory effect, both macroscopically and biochemically) superiority for the nano-liposomal drug above the free prednisolone in rats.     

Hippocampal activation during a cognitive task is associated with subsequent neuroendocrine and cognitive responses to psychological stress

Increased activation of the hypothalamus pituitary adrenal (HPA) axis, marked by increased secretion of cortisol, is a biological marker of psychological stress. It is well established that the hippocampus plays an important role in the regulation of HPA axis activity. The relationship between cortisol (stress‐related elevation or exogenous administration) and the hippocampal‐related cognitive function is often examined. However, few human studies to date have examined the effect of stress on hippocampal activity and the interactions between stress‐induced activation of the HPA axis and hippocampal function during different phases of cognitive function. On the basis of our previous work, we hypothesized that group differences in stress‐sensitivity relate to differences in hippocampal‐related stress‐integration. To test this hypothesis, we conducted a functional MRI study using tasks known to involve the hippocampal formation: novel‐picture encoding, psychological stress, and paired‐picture recognition. On the basis of their cortisol responses to stress, we divided subjects into stress‐responders (increase in cortisol, n = 9) and nonresponders (decrease in cortisol, n = 10). Responders showed higher hippocampal deactivation during the stress task and lower recognition scores due to a larger number of misses. Intriguingly, stress‐responders showed significant differences in hippocampal activation already prior to stress, with higher levels of hippocampal activity during the picture encoding. Although effects of both cortisol and hippocampal activation on recognition were present in responders, similar effects were absent in the nonresponder group. Our results indicate that hippocampus plays an important role in adaptive behavioral responses. We hypothesize that states of hippocampal activation prior to stress might reflect states of vigilance or anxiety, which might be important for determining interindividual differences in subsequent stress response and cognitive performance. © 2009 Wiley‐Liss, Inc.     

Effect of transcranial near-infrared photobiomodulation on cognitive outcomes in D-galactose/AlCl3 induced brain aging in BALB/c mice

Lasers in Medical Science - Brain photobiomodulation (PBM) therapy (PBMT) modulates various biological and cognitive processes in senescence rodent models. This study was designed to investigate...     

From the Cover: Herded and hunted goat genomes from the dawn of domestication in the Zagros Mountains

The Aceramic Neolithic (∼9600 to 7000 cal BC) period in the Zagros Mountains, western Iran, provides some of the earliest archaeological evidence of goat (Capra hircus) management and husbandry by circa 8200 cal BC, with detectable morphological change appearing ∼1,000 y later. To examine the genomic imprint of initial management and its implications for the goat domestication process, we analyzed 14 novel nuclear genomes (mean coverage 1.13X) and 32 mitochondrial (mtDNA) genomes (mean coverage 143X) from two such sites, Ganj Dareh and Tepe Abdul Hosein. These genomes show two distinct clusters: those with domestic affinity and a minority group with stronger wild affinity, indicating that managed goats were genetically distinct from wild goats at this early horizon. This genetic duality, the presence of long runs of homozygosity, shared ancestry with later Neolithic populations, a sex bias in archaeozoological remains, and demographic profiles from across all layers of Ganj Dareh support management of genetically domestic goat by circa 8200 cal BC, and represent the oldest to-this-date reported livestock genomes. In these sites a combination of high autosomal and mtDNA diversity, contrasting limited Y chromosomal lineage diversity, an absence of reported selection signatures for pigmentation, and the wild morphology of bone remains illustrates domestication as an extended process lacking a strong initial bottleneck, beginning with spatial control, demographic manipulation via biased male culling, captive breeding, and subsequently phenotypic and genomic selection.

The initial domestication of southwest Asian crops and livestock species unfolded across the Fertile Crescent after the end of the Younger Dryas climatic downturn circa 9600 BC and coalesced into fully integrated agricultural economies by 7500 cal BC (1). Until recently, the western part of this region was cast as the epicenter of this transition, while the Zagros Mountains, at the eastern end of the Fertile Crescent, was considered a backwater, slow to receive and embrace domesticates and food-producing technologies from farther west (2, 3). However, this region of western Iran has been recently postulated as a primary center for the domestication of a number of plant and animal species (4), including barley (5, 6), possibly emmer wheat (7), several pulse species (8), and most notably, goats (9). This latter hypothesis has been supported by ancient genomic data, which indicate that the eastern Fertile Crescent was one of three regions key in shaping the Neolithic goat gene pool (10).Here we explore the transition from the hunting of wild bezoar goats (Capra aegagrus) to their initial management and subsequent domestication in the eastern Fertile Crescent by combining ancient genome sequencing and archaeozoological evidence from Ganj Dareh and Tepe Abdul Hosein, two sites in the central Zagros dating to the early or Aceramic Neolithic (AN) circa 8000 cal BC. These genomic data present a singular opportunity to deepen our understanding of the consequences of goat management at the dawn of domestication.