Most clinical trial participants feel they have a right to study result disclosure, regardless of trial outcome. In-person visits are preferred for negative results, but more feasible alternatives such as letters were still acceptable for the majority of participants. However, Internet-based disclosure was not acceptable to most participants in oncology trials. Time and cost allocations for result disclosure should be considered during grant and ethics board applications, and clear guidelines are required to help researchers share the results with patients.
Background and purposeReovirus is a ubiquitous RNA virus that exploits aberrant signaling pathways for its replication. The oncolytic potential of reovirus against numerous cancers under pre-clinical/clinical conditions has been documented by us and others. Despite its proven clinical activity, the underlying mechanisms of reovirus oncolysis is still not well elucidated. If reovirus therapy is to be optimized for cancer, including breast cancer patients, it is imperative to understand the mechanisms of reovirus oncolysis, especially in treatment of resistant tumour.Experimental approach and resultsIn the present study global gene expression profiling was utilized as a preliminary roadmap to tease-out pivotal molecules involved in reovirus induced apoptosis in breast cancer. Reovirus treated HTB133 and MCF7 breast cancer cells revealed transcriptional alteration of a defined subset of apoptotic genes and members of the nuclear factor-kappa B (NF-kB) family and p53 upregulated modulator of apoptosis (PUMA) were prominent. Since NF-kB can paradoxically suppress or promote apoptosis in cancer, the significance of NF-kB in reovirus oncolysis of breast cancer was investigated. Real time PCR analysis indicated a 2.9–4.3 fold increase in NF-kB p65 message levels following reovirus infection of MCF7 and HTB133, respectively. Nuclear translocation of NF-kB p65 protein was also dramatically augmented post reovirus treatment and correlated with enhanced DNA binding. Pharmacologic inhibition of NF-kB lead to oncolytic protection and significant down regulation of PUMA message levels. PUMA down regulation using siRNA suppressed reovirus oncolysis via significantly repressed apoptosis in p53 mutant HTB133 cells.ConclusionsThis study demonstrates for the first time that a prominent pathway of reovirus oncolysis of breast cancer is mediated through NF-kB and that PUMA upregulation is dependent on NF-kB activation. These findings represent potential therapeutic indicators of reovirus treatment in future clinical trials.
Advanced robotic devices capable of simulating the dexterous ability of the upper limb with an array of internal sensors have raised the enticing prospect of replacing the lost intricate functions of the arm following upper limb amputation. However, a large gap still exists in the application of this technology to the human user. In particular, the ability to provide physiologically relevant sensory feedback-to have the amputee feel the prosthetic hand as their own-has not yet been achieved. Although a number of different approaches are being investigated, targeted sensory reinnervation, a refinement of the original targeted muscle reinnervation procedure, is the most recent and promising development in the effort to create a functional human-machine interface with a closed loop sensory feedback system. This technique aims to reestablish hand sensation on the skin so that it can be readily accessed non-invasively during functional tasks. Recent efforts are being directed towards distributing hand maps widely on the stump without interference of sensations from the native area. In this article, we will review the surgical approaches that have been used for sensory reinnervation in upper arm amputation and compare the resultant outcomes and potential functional utility of the techniques.
he majority of chest wall defects requiring reconstruction are secondary to ablation for primary chest wall tumors, locally invasive breast or lung tumors, and metastatic lesions. 1 Other indications for chest wall reconstruction include trauma, infection, radiation-induced ulceration and necrosis leading to exposed hardware, mediastinitis, bronchopleural fistula, and empyema. 1-3 A recent review of an 81-patient cohort from 2003 to 2014 reported indications for chest wall resection and reconstruction to be primarily oncologic (61 percent of patients), and a minority for desmoid tumors (12 percent), bronchopleural fistula (4 percent), infection (9 percent), and anatomical deformity (9 percent) (Level of Evidence: Therapeutic, IV). 3 A previous study of 200 chest wall resections from 1975 to 2000 similarly highlighted reconstructive indications for primary lung cancer with extension into the chest wall (38 percent of patients), primary chest wall tumors (27 percent), breast
Autologous breast reconstruction using abdominal-based perforator flaps produces excellent aesthetic results with minimal donor site morbidity. The superficial inferior epigastric artery and deep inferior epigastric perforator (DIEP) flaps reliably perfuse a hemi-abdomen, up to the anterior axillary line. Beyond this line laterally, the flank or "love handle" tissue is primarily perfused by the deep circumflex iliac artery (DCIA) or secondarily by the superficial circumflex iliac artery. The flank tissue is a valuable addition to increase flap size when harvested with a DIEP flap or to provide vascularized tissue when the abdomen has been previously harvested. Harvesting the flank tissue in combination with the anterior abdominal tissue improves the contour of the trunk, accentuates the waist, and minimizes secondary revisions to excise prominent "dogears." The DCIA flap is a novel technique for breast reconstruction. In this article, we describe our technique, pearls and pitfalls, and early results. Résumé La reconstruction mammaire autologue à l'aide de lambeaux perforateurs abdominaux produit d'excellents résultats esthétiques et une morbidité minimale au siège du donneur. Les lambeaux de l'artèreépigastrique inférieure superficielle et du perforateuŕ epigastrique inférieur profond (PÉIF) perfusent en toute fiabilité un hémi-abdomen, jusqu'à la ligne axillaire antérieure. Au-delà de cette ligne latérale, la perfusion primaire des tissus du flanc, ou de la « poignée d'amour », est d'abord assurée par l'artère iliaque circonflexe profonde (AICP) ou secondairement par l'artère iliaque circonflexe superficielle. Les tissus du flanc sont un ajout précieux à l'accroissement de la dimension du lambeau lorsqu'il est prélevé avec un lambeau du PÉIF ou qu'il vise à fournir des tissus vascularisés après avoirété prélevé dans l'abdomen. Le prélèvement des tissus du flanc en combinaison avec les tissus abdominaux antérieurs améliore le contour du tronc, accentue la taille et réduit les révisions secondaires pour exciser les « oreilles de chien » proéminentes. Le lambeau de l'AICP est une nouvelle technique de reconstruction mammaire. Dans le présent article, les auteurs décrivent leur technique, leurs perles et leursécueils de même que leurs résultats préliminaires.
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