Effect of Talactoferrin Alfa on the Immune System in Adults With Non‐Small Cell Lung Cancer

Background.

Talactoferrin alfa (talactoferrin), an agent with immune-stimulating properties, has demonstrated safety and preliminary efficacy in clinical trials.

Methods.

Ten patients (five males and five females) with stage IV non-small cell lung cancer (NSCLC) in a single-arm pilot study received orally administered talactoferrin (1.5 g, b.i.d.) for up to 24 weeks. Radiographic and immunologic studies were performed at baseline and at weeks 6 and 12. Circulating immune cells (natural killer cells [NKCs], CD4⁺, CD8⁺, and regulatory T cells) and systemic cytokine levels were measured to assess immune response.

Results.

Patients enrolled in the study had received a median of four prior chemotherapy regimens, and all patients were symptomatic. Talactoferrin was well tolerated, with no grade 3 or 4 toxicities. Median time to progression (TTP) and overall survival were 6 weeks and 14.5 weeks, respectively. The four patients with ≥9 weeks TTP had evidence of immunologic activity (three with increased NKC activity).

Conclusions.

The median of four previous chemotherapy regimens, with elevated levels of interleukin (IL) 6 and tumor necrosis factor-alfa in most patients, suggests these patients were poor candidates for immunotherapy.     

Immunotherapy in prostate cancer: emerging strategies against a formidable foe

Recent clinical trials have shown therapeutic vaccines to be promising treatment modalities against prostate cancer. Unlike preventive vaccines that teach the immune system to fight off specific microorganisms, therapeutic vaccines stimulate the immune system to recognize and attack certain cancer-associated proteins. Additional strategies are being investigated that combine vaccines and standard therapeutics, including radiation, chemotherapy, targeted therapies, and hormonal therapy, to optimize the vaccines’ effects. Recent vaccine late-phase clinical trials have reported evidence of clinical benefit while maintaining excellent quality of life. One such vaccine, sipuleucel-T, was recently FDA-approved for the treatment of metastatic prostate cancer. Another vaccine, PSA-TRICOM, is also showing promise in completed and ongoing randomized multicenter clinical trials in both early- and late-stage prostate cancer. Clinical results available to date indicate that immune-based therapies could play a significant role in the treatment of prostate and other malignancies.     

Apo material as a trigger for inflammation in systemic lupus erythematosus

While several characteristics of systemic lupus erythematosus (SLE) have been investigated, the distinct pathogenetic mechanisms leading to autoimmunity and chronic inflammation are not understood yet. A central role for apo has been implicated in the pathogenesis of SLE and an increased rate of apo or a defective clearance of apo cells have repeatedly been described in SLE patients, which show elevated levels of alpha-interferon (αIFN) as well as an enhanced expression of αIFN-alpha inducible genes referred to as αIFN signature. Recent publications link αIFN and apo: apo cell-derived microparticles can directly stimulate plasmacytoid dendritic cells to secret αIFN. This review highlights the role of apo material as source for AAg and as a trigger for chronic inflammation in the pathogenesis of SLE.     

No short-term effects of calorie-controlled Mediterranean or fast food dietary interventions on established biomarkers of vascular or metabolic risk in healthy individuals

BACKGROUND/OBJECTIVES

This study addressed the question whether the composition of supposedly ''healthy'' or ''unhealthy'' dietary regimes has a calorie-independent short-term effect on biomarkers of metabolic stress and vascular risk in healthy individuals.

SUBJECTS/METHODS

Healthy male volunteers (age 29.5 ± 5.9 years, n = 39) were given a standardized baseline diet for two weeks before randomization into three groups of different dietary regimes: fast food, Mediterranean and German cooking style. Importantly, the amount of calories consumed per day was identical in all three groups. Blood samples were analyzed for biomarkers of cardiovascular risk and metabolic stress after two weeks of the baseline diet and after two weeks of the assigned dietary regime.

RESULTS

No dietary intervention affected the metabolic or cardiovascular risk profile when compared in-between groups or compared to baseline. Subjects applied to the Mediterranean diet showed a statistically significant increase of uric acid compared to baseline and compared to the German diet group. Plasma concentrations of urea were significantly higher in both the fast food group and the Mediterranean group, when compared to baseline and compared to the German diet group. No significant differences were detected for the levels of vitamins, trace elements or metabolic stress markers (8-hydroxy-2-deoxyguanosine, malondialdehyde and methylglyoxal, a potent glycating agent). Established parameters of vascular risk (e.g. LDL-cholesterol, lipoprotein(a), homocysteine) were not significantly changed in-between groups or compared to baseline during the intervention period.

CONCLUSIONS

The calorie-controlled dietary intervention caused neither protective nor harmful short-term effects regarding established biomarkers of vascular or metabolic risk. When avoiding the noxious effects of overfeeding, healthy individuals can possess the metabolic capacity to compensate for a potentially disadvantageous composition of a certain diet.     

High-resolution human genome structure by single-molecule analysis

Variation in genome structure is an important source of human genetic polymorphism: It affects a large proportion of the genome and has a variety of phenotypic consequences relevant to health and disease. In spite of this, human genome structure variation is incompletely characterized due to a lack of approaches for discovering a broad range of structural variants in a global, comprehensive fashion. We addressed this gap with Optical Mapping, a high-throughput, high-resolution single-molecule system for studying genome structure. We used Optical Mapping to create genome-wide restriction maps of a complete hydatidiform mole and three lymphoblast-derived cell lines, and we validated the approach by demonstrating a strong concordance with existing methods. We also describe thousands of new variants with sizes ranging from kb to Mb.     

Therapeutic cancer vaccines: the latest advancement in targeted therapy

Therapeutic cancer vaccines represent an emerging therapeutic modality that may play a more prominent role in cancer treatment in the future. Therapeutic cancer vaccines are designed to generate a targeted, immune-mediated antitumor response. There are 2 main types of therapeutic vaccines: patient-specific (generated either from a patient's own cells or tumor) and patient- nonspecific, where a peptide- or vector-based vaccine induces an immune response in vivo against specific tumor-associated antigens. Studies are currently underway to investigate methods to enhance vaccine strategies, including combinations with standard anticancer therapies or immune-modulating agents. Cancer vaccines are usually well tolerated, with minimal toxicity compared with chemotherapy. This review summarizes selected therapeutic cancer vaccines in late clinical development.     

Program at Home: A Veterans Affairs Healthcare Program to Deliver Hospital Care in the Home

The Portland Veterans Affairs Medical Center (PVAMC) participated in a research‐based National Demonstration and Evaluation Study of Hospital at Home Care for Elderly Patients. PVAMC continued hospital at home care in a modified form based on the results of that research phase and feedback from patients, families, and staff. The modified clinical program (referred to as Program @ Home) provided care for the same diagnoses (exacerbation of congestive heart failure, exacerbation of chronic obstructive pulmonary disease, community‐acquired pneumonia, cellulitis) but differed from the research‐based demonstration project in that it accepted patients of all ages, accepted early‐discharge patients from the hospital, and provided a less‐intensive physician and nursing model. In the first 42 months, 290 patients were admitted; 23% came from the emergency room, 54% were early hospital discharge, and the remainder came from an outpatient clinic or home care. Average length of stay was 3.2 days, and 37% were younger than 65. The results describe how a home hospital program has been integrated into the clinical care offerings of a managed care health system and how it supports inpatient, primary, emergency, and home care programs.     

Unit Support Protects Against Sexual Harassment and Assault Among National Guard Soldiers

ObjectiveDespite concerns about increased sexual harassment and assault after the 2013 legislation repealing the ban on women in combat, little research has examined military factors that could prevent sexual harassment and assault during deployment. This study examined whether unit support, which reflects the quality of service members' relationships within their unit, protects against sexual harassment and assault during deployment.MethodsParticipants were 1,674 Ohio Army National Guard service members who reported at least one deployment during a telephone survey conducted in 2008 and 2009. Participants completed measures of sexual harassment/assault, unit support, and psychosocial support. Logistic regression was used to model odds of sexual harassment/assault.ResultsApproximately 13.2% of men (n = 198) and 43.5% of women (n = 74) reported sexual harassment, and 1.1% of men (n = 17) and 18.8% of women (n = 32) reported sexual assault during their most recent deployment. Greater unit support was associated with decreased odds of sexual harassment and assault.ConclusionsA substantial proportion of men and women reported sexual harassment/assault. Greater unit support was associated with diminished odds of sexual harassment/assault during deployment. Programming designed to improve unit cohesion has the potential to reduce sexual harassment and assault.     

Actions of Phenylephrine, Isoproterenol, and Epinephrine Halothane on Endocardial Conduction and Activation in Canine Left Ventricular Papillary Muscles

Background: Myocardial sensitization by halothane to the arrhythmogenic effects of epinephrine involves synergistic actions mediated by alpha1 - and beta-adrenoceptors. Halothane potentiates a transient alpha1 -adrenoceptor-mediated negative dromotropic effect of epinephrine on Purkinje fibers. This study examines how halothane alters the actions of alpha1 - and beta-agonists and epinephrine on endocardial conduction.

Methods: Superfused canine papillary muscles were mapped to locate a Purkinje-ventricular muscle junction (PVJ), and bipolar electrodes were placed to measure Purkinje and endocardial conduction velocity and PVJ conduction time during stimulation of the Purkinje layer. The effects of exposure to 5 micro Meter phenylephrine, 1 micro Meter isoproterenol, or 5 micro Meter epinephrine on conduction were determined in the absence and presence of 0.4 mM halothane in three groups of 10 preparations.

Results: Isoproterenol slightly increased Purkinje conduction velocity and markedly improved conduction at the PVJ and in the endocardium similarly in the presence or absence of halothane. Phenylephrine depressed Purkinje velocity (-12%) only in the presence of halothane and did not slow conduction at the PVJ or in the myocardium. Epinephrine transiently depressed Purkinje velocity, more so with (-22%) than without (-12%) halothane (P 相似文献