Functional analysis of LAT3 in prostate cancer: Its downstream target and relationship with androgen receptor

L-type amino acid transporter 3 (LAT3, SLC43A1) is abundantly expressed in prostate cancer (PC) and is thought to play an essential role in PC progression through the cellular uptake of essential amino acids. Here, we analyzed the expression, function, and downstream target of LAT3 in PC. LAT3 was highly expressed in PC cells expressing androgen receptor (AR), and its expression was increased by dihydrotestosterone treatment and decreased by bicalutamide treatment. In chromatin immunoprecipitation sequencing of AR, binding of AR to the SLC43A1 region was increased by dihydrotestosterone stimulation. Knockdown of LAT3 inhibited cell proliferation, migration, and invasion, and the phosphorylation of p70S6K and 4EBP-1. Separase (ESPL1) was identified as a downstream target of LAT3 by RNA sequencing analysis. In addition, immunostaining of prostatectomy specimens was performed. In the multivariate analysis, high expression of LAT3 was an independent prognostic factor for recurrence-free survival (hazard ratio: 3.24; P = .0018). High LAT3 expression was correlated with the pathological T stage and a high International Society of Urological Pathology grade. In summary, our results suggest that LAT3 plays an important role in the progression of PC.     

Dopamine agonist‐induced antecollis in Parkinson's disease

Few cases of dopamine agonist‐induced antecollis in Parkinson's disease (PD) have been reported. Literature review of 16 PD patients including our 3 cases with dopamine agonist‐induced antecollis showed predominance of (1) Japanese, (2) women, and (3) Hoehn‐Yahr stage of ≥3. We experienced three Japanese PD patients who subacutely exhibited antecollis following increased dopamine agonist dose that improved just after withdrawal of the agonist. One patient developed antecollis during increasing pramipexole dose in combination with cabergoline. Antecollis in another patient appeared during increasing pramipexole dose; it worsened after substituting pergolide for pramipexole, but improved after withdrawal of pergolide. Our cases indicate that there is no specific dopamine agonist causing antecollis, and it is possibly caused by a number of single dopamine agonists or a combination of them. Dopamine agonist‐induced antecollis should be considered when encountering antecollis in PD patients being treated with dopamine agonists and withdrawal of the agonist can improve symptoms. © 2009 Movement Disorder Society     

Two cases of stereotactic radiosurgical boost as an initial treatment for young nasopharyngeal cancer patients

Case 1: A 14-year-old boy with nasopharyngeal cancer (T4N0M0) was treated with stereotactic radiosurgery (SRS) as a boost therapy after conventional radiotherapy. Persistent residual tumor visible with MR remained after conventional radiotherapy comprising 59.6 Gy in total. We therefore performed SRS to add a further irradiation dose while causing minimal damage to adjacent normal tissue. SRS was performed using multiple non-coplanar arcs delivered to the residual tumor, which was defined to add 2 mm margins to the residual tumor. This was 30 cc as defined by CT and MR images. Twenty Gy were administered to the periphery of the planning target volume (PTV), corresponding to the 80% isodose line. No recurrences or late complications have been observed 4 years and 6 months after the SRS. Case 2: A 27-year-old man with nasopharyngeal cancer (T1N0M0) was treated with SRS as a boost therapy following conventional radiotherapy with 55 Gy. The SRS was performed using multiple non-coplanar arcs delivered to the PTV, which was 10 cc as defined by CT and MR images as in case 1. Sixteen Gy were administered to the periphery of the residual tumor, corresponding to the 80% isodose line. The tumor was not visible on follow-up MR images and no complications have been observed 4 years and 2 months after the SRS.