The Role of Brain Tumor Advocacy Groups

The brain tumor community is a unique, underserved population that has not seen significant improvements in survival over the last four decades. In the search for effective treatments for brain tumors, nonprofit patient advocacy organizations identify and fill the gaps that the for-profit sector and the government have not addressed or cannot address. Although many articles have been written on the roles of patient advocacy groups in general, or in targeted areas such as clinical trial recruitment, none have looked at the brain tumor community specifically. This review looks at the literature on patient advocacy groups and provides specific examples of brain tumor advocacy organizations that offer these services. It examines the evolution of the role of these organizations over time, and how that has been reflected in the programs and services provided. This is a collaborative effort to highlight programs and services across multiple patient advocacy organizations.     

Prnp gene and cerebellum volume in patients with refractory mesial temporal lobe epilepsy

The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection, neuroplasticity and neurodevelopment. The variant allele Valine at codon 129 of the Prnp was associated with decreased brain volume in healthy volunteers and schizophrenic patients. We investigate the association between the cerebellum volume and the presence of variant allele Valine at codon 129 of the Prnp gene in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). The Prnp coding sequence was determined in 41 refractory MTLE-HS patients. The cerebellum volume corrected by the intracranial volume of patients with the normal Prnp genotypes was compared with that of patients presenting the variant alleles at codon 129. Twenty patients showed the Met129Met genotype, 16 showed Met129Val, and 5 had Val129Val. There were no association among clinical, demographic, electrophysiological, antiepileptic drugs used, and the presence of the Prnp variant alleles. The presence of Prnp variant allele at codon 129 was not associated with the analyzed cerebellum volume. Prnp variant alleles at codon 129 are not associated with cerebellum volume in patients with refractory MTLE-HS.     

Long-term decrease in Na,K-ATPase activity after pilocarpine-induced status epilepticus is associated with nitration of its alpha subunit

Temporal lobe epilepsy (TLE) is the most common type of epilepsy with about one third of TLE patients being refractory to antiepileptic drugs. Knowledge about the mechanisms underlying seizure activity is fundamental to the discovery of new drug targets. Brain Na⁺,K⁺-ATPase activity contributes to the maintenance of the electrochemical gradients underlying neuronal resting and action potentials as well as the uptake and release of neurotransmitters. In the present study we tested the hypothesis that decreased Na⁺,K⁺-ATPase activity is associated with changes in the alpha subunit phosphorylation and/or redox state. Activity of Na⁺,K⁺-ATPase decreased in the hippocampus of C57BL/6 mice 60 days after pilocarpine-induced status epilepticus (SE). In addition, the Michaelis–Menten constant for ATP of α2/3 isoforms increased at the same time point. Nitration of the α subunit may underlie decreased Na⁺,K⁺-ATPase activity, however no changes in expression or phosphorylation state at Ser⁹⁴³ were found. Further studies are necessary define the potential of nitrated Na⁺,K⁺-ATPase as a new therapeutic target for seizure disorders.     

Clinical efficacy and tolerability of an immune-stimulant<Superscript>*</Superscript> constituted by inactivated bacterial bodies in the prophylaxis of infectious episodes of airways: a double blind,placebo-controlled,randomized, multicentre study

Background

(Buccalin ®) is a Bacterial Lysates (BL) that belongs to a family of immune-stimulators, developed more than 30 years ago and it still has a role in the prophylaxis of Recurrent Respiratory Tract Infections (RRTI). However, original studies were conducted with an approach that does not seem to be aligned with the present methodologies. In addition, concomitant therapies substantially improved in the last decades. These two reasons strongly suggested to update our knowledge on the capacity of this bacterial lysate (Buccalin ®) to reduce the number of days with infectious episodes in patients with RRTI.

Methods

A double blind, placebo-controlled, randomized, multicentre study was programmed (EudraCT code: 2011-005187-25). The reduction of the number of days with infectious episodes (IE) was the primary endpoint. Secondary endpoints were the number of IE, the use of concomitant drugs, the efficacy on signs and symptoms of RRTI and the safety of the drug. Patients were treated according to the registered schedule and were followed up for a period of 6 months.

Results

From a cohort of 188 patients eligible for the study, 90 were included in the active group and 88 in the placebo group. The study was completed in 170 patients. A significant reduction of the number of days with IE was observed (6.57 days in the active group and 7.47 in the placebo group). Secondary endpoints were only partially achieved. No virtual adverse events related to the treatment were recorded.

Conclusion

The administration of bacterial lysate (Buccalin ®) in patients with RRTI had the capacity to significantly reduce the number of days with IE in a multicentre, randomized, placebo controlled, clinical study. The treatment was safe. Of note, all patients were free to be treated with the best concomitant therapies. In these conditions, the positive results observed demonstrated that this bacterial lysate has maintained its capacity of reducing the days with infections in patients with RRTI, also in association to the concomitant therapies available nowadays.

     

Innervation zone locations in 43 superficial muscles: Toward a standardization of electrode positioning

Introduction: We describe the innervation zone (IZ) location in 43 muscles to provide information for appropriate positioning of bipolar electrodes for clinical and research applications. Methods: The IZ was studied in 40 subjects (20 men and 20 women) using multichannel surface electromyography (sEMG). Signal quality was checked visually to identify motor unit action potentials and estimate muscle fiber conduction velocity. Results: Results in 33 muscles were classified as excellent or good, because it was possible to identify an area which is favorable for appropriate positioning of an electrode pair without the need to previously determine the IZ location. Conclusions: Knowledge of IZ location will increase standardization and repeatability of sEMG measures. Muscle Nerve 49 :413–421, 2014     

Adoptive transfer of chimeric FcepsilonRI gene-modified human T cells for cancer immunotherapy

Immunotherapeutic approaches involving genetic modification of T cells show promise in generating highly specific tumor-reactive effector cells for cancer treatment. Given the high affinity of FcRI (the subtype I Fc receptor for IgE) for IgE monoclonal antibody (mAb), modification of T cells with chimeric FcRI in combination with tumor-specific IgE mAbs is potentially a powerful and effective strategy to specifically target T cells to tumor cells. In this study, we retrovirally transduce human primary T cells with a cDNA encoding the extracellular domain of FcRI linked to the hinge and transmembrane domains of FcRI and the cytoplasmic domains of CD28 and T cell receptor zeta chain (FcRI-CD28-zeta). We demonstrate that human T cells expressing FcRI-CD28-zeta, in the presence of tumor-specific IgE mAb recognizing mouse CD8 antigen (Ly- 2.1+), can specifically secrete cytokine, proliferate, and mediate cytotoxic function after antigen ligation. Furthermore, adoptive transfer of FcRI-CD28-zeta cells incubated with anti-Ly-2.1 IgE mAb significantly enhances the survival of irradiated nonobese diabetic-severe combined immunodeficiency mice bearing Ly-2.1+ tumor compared with control mice. Thus, this set of experiments demonstrates that Fc gene-engineered human T cells mediate effector function in vitro and in vivo in an IgE-dependent manner and thus a novel and valid approach for cancer therapy can now be further developed.     

Management of Positive Sub‐areolar/Nipple Duct Margins in Nipple‐Sparing Mastectomies

We evaluated management of positive sub‐areolar/nipple duct margins in nipple‐sparing mastectomies (NSM) at our institution. Retrospective chart review of all NSM from January 2007 to April 2012 was performed and patient, tumor, and treatment information was collected. Sub‐areolar/nipple duct margins included ductal tissue from within the nipple. Of 438 NSM, 22 (5%) had positive sub‐areolar/nipple duct margins; 21 of 220 cancer‐bearing breasts (10%) and 1 of 218 prophylactic mastectomies (0.5%). Positive margins included four with invasive lobular carcinoma and 18 with ductal carcinoma in situ (DCIS). Management included removal of eight nipples and nine nipple areola complexes (NAC). Four of 17 nipple/NAC specimens had evidence of residual DCIS and none had residual invasive cancer. The majority of nipple/NAC specimens excised for a positive margin had no residual malignancy. Future studies are needed to determine the extent of NAC tissue removal required for positive margins.