Kathy Li

Physician Expectations of Treatment Outcomes for Patients With Brain Metastases Referred for Whole Brain Radiotherapy

PURPOSE Patients with advanced cancer are referred to our Rapid Response Radiotherapy Program for quick access to palliative radiotherapy. The primary objective of this prospective study was to determine the physician expectations of the treatment outcomes for patients with brain metastases referred for whole brain radiotherapy (WBRT). The secondary objectives were to determine the factors influencing the expectations and to examine the accuracy of the physician-estimated patient survival. METHODS AND MATERIALS Patients were identified during a 17-month period. The referring physicians were sent a survey by facsimile to be completed and returned before the patient consultation. Information was sought on the patients disease status, the physicians expectations of WBRT, the estimated patient survival and performance status, and physician demographic data. RESULTS A total of 137 surveys were sent out, and the overall response rate was 57.7%. The median patient age was 66 years (range, 35-87), 78.5% had multiple brain metastases, 42.3% had a controlled primary tumor, and 62.3% had extracranial disease. WBRT was thought to stabilize neurologic symptoms, improve quality of life, and allow for a Decadron (dexamethasone) taper by > or =94.9% of the referring physicians; 87.0% thought WBRT would improve performance status; 77.9% thought it would improve neurologic symptoms; and 40.8% thought it would improve survival. The referring physicians estimated patient survival as a median of 6.0 months; however, the actual survival was a median of 2.5 months, for a median individual difference of 1.9 months (p < .0001). CONCLUSION Physicians referring patients with brain metastases for consideration of WBRT are often overly optimistic when estimating the clinical benefit of the treatment and overestimate patient survival. These findings highlight the need for education and additional research in this field.

De Novo Protein Synthesis of Syntaxin-1 and Dynamin-1 in Long-Term Memory Formation Requires CREB1 Gene Transcription in Lymnaea stagnalis

Consolidation of aversive operant conditioning into long-term memory (LTM) requires CREB-dependent de novo protein synthesis. The newly synthesized proteins are distributed to the synapses in neurons that are involved in memory formation and storage. Accumulating evidence indicates that the presynaptic release mechanisms also play a role in long-term synaptic plasticity. Our understanding of whether the presynaptic proteins undergo de novo synthesis during long-term memory formation is limited. In this study, we investigated the involvement of syntaxin-1, a presynaptic exocytotic protein, and dynamin-1, an endocytotic protein, in the formation of long-term memory. We took advantage of a well-established aversive operant conditioning model of aerial respiratory behavior in the fresh water pond snail Lymnaea stagnalis, and demonstrated that the LTM formation is associated with increased expression of syntaxin-1 and dynamin-1, coincident with elevated levels of CREB1. Partial knockdown of CREB1 gene by double stranded RNA inhibition (dsRNAi) prior to operant conditioning prevented snails from memory consolidation, and reduced the expression of syntaxin-1 and dynamin-1 at both mRNA and protein levels. These findings suggest that CREB1-mediated gene expression is required for the LTM-induced up-regulation of synaptic proteins, syntaxin-1 and dynamin-1, in L. stagnalis. Our study thus offers new insights into the molecular mechanisms that mediate CREB1-dependent long-term memory formation.

Reasons for Poor Accrual in Palliative Radiation Therapy Research Studies

BACKGROUND Patients with advanced-stage cancer commonly have multiple symptoms, poor performance status, and limited life expectancies. Despite the need for evidence-based practice and guidelines for palliative radiation therapy (RT), conducting clinical palliative research has proven to be a challenge in the past because of low accrual rates and high patient attrition. We explore the change in accrual rates, reasons for nonparticipation in palliative RT clinical research trials, and factors that contributed to the increase in accrual over a 3-year period. PATIENTS AND METHODS A record was kept for all patients seen at the Rapid Response Radiotherapy Program between 2002 and 2005, including information on patient demographics, disease characteristics, and whether patients were accrued into >/=1 palliative research study at the time of clinic visit. If a patient did not participate in a study, the reason for nonaccrual was recorded. RESULTS Despite previous difficulties, changes to the methods of conducting palliative research and study design have resulted in an increase in patient accrual, from 14% to an average of approximately 60%. The implementation of a full-time clinical research assistant and a simple study design with realistic eligibility criteria contributed to the increase in patient participation. CONCLUSION Difficulties in conducting palliative clinical research trials were improved through changes in study design and research administration. Future clinics should use a dedicated clinical research assistant responsible for patient recruitment and study management. Studies should be designed specifically for the patient population receiving palliative care and should involve clearly defined and realistic eligibility criteria and brief assessments.

MEN1 Tumor Suppressor Gene is Required for Long-term Memory Formation in an Aversive Operant Conditioning Model of Lymnaea stagnalis

Activity-dependent transcription factors critically coordinate the gene expression program underlying memory formation. The tumor suppressor gene, MEN1, encodes a ubiquitously expressed transcription regulator required for synaptogenesis and synaptic plasticity in invertebrate and vertebrate central neurons. In this study, we investigated the role of MEN1 in long-term memory (LTM) formation in an aversive operant conditioning paradigm in the freshwater pond snail Lymnaea stagnalis (L. stagnalis). We demonstrated that LTM formation is associated with an increased expression of MEN1 coinciding with an up-regulation of creb1 gene expression. In vivo knockdown of MEN1 prevented LTM formation and conditioning-induced changes in neuronal activity in the identified pacemaker neuron RPeD1. Our findings suggest the involvement of a new pathway in LTM consolidation that requires MEN1-mediated gene regulation.