ABSTRACT
RATIONALE: Impulsive aggressive personality disordered patients have been shown to have decreased relative glucose metabolism in orbito-frontal cortex and anterior cingulate gyrus compared with normal subjects. In addition, patients with impulsive aggression have an attenuation of symptoms with selective serotonin reuptake inhibitor (SSRI) treatment. OBJECTIVES: The goals of the present study were to attempt to replicate the finding of improvement in impulsive aggression in borderline personality disorder with SSRIs and to investigate the specific cortical areas modified by medication, which might underlie the observed clinical improvement using (18)FDG-PET. METHODS: Ten impulsive aggressive patients with borderline personality disorder were imaged with (18)F-deoxyglucose positron emission tomography at baseline and after receiving fluoxetine at 20 mg/day for 12 weeks. Anatomical MRIs were coregistered to PET and relative metabolic rates were obtained in 39 Brodmann areas. RESULTS: Brodmann areas 11 and 12 in the orbito-frontal cortex showed significant increases in relative metabolic rate. Significant clinical improvement was also observed as assessed by the Overt Aggression Scale-Modified. CONCLUSIONS: These changes are consistent with a normalizing effect of fluoxetine on prefrontal cortex metabolism in impulsive aggressive disorder.
Subject(s)
Aggression/physiology , Antidepressive Agents, Second-Generation/therapeutic use , Fluoxetine/therapeutic use , Impulsive Behavior/metabolism , Prefrontal Cortex/metabolism , Adult , Aggression/drug effects , Aggression/psychology , Antidepressive Agents, Second-Generation/adverse effects , Double-Blind Method , Female , Fluorodeoxyglucose F18 , Fluoxetine/adverse effects , Humans , Image Processing, Computer-Assisted , Impulsive Behavior/diagnostic imaging , Impulsive Behavior/psychology , Magnetic Resonance Imaging , Male , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/drug effects , Psychiatric Status Rating Scales , Radionuclide Imaging , RadiopharmaceuticalsABSTRACT
PURPOSE: KLK15 is a newly cloned human kallikrein gene. Many kallikreins were found to be differentially expressed in ovarian cancer. Like other kallikreins, KLK15 is regulated by steroid hormones in cancer cell lines. KLK15 is upregulated mainly by androgens and to a lesser extent by progestins. The purpose of this study was to examine the prognostic value of KLK15 in ovarian cancer tissues. MATERIALS AND METHODS: We studied KLK15 expression by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in 168 consecutive patients with epithelial ovarian cancer. Ten patients with benign ovarian tumors were also included in the study. An optimal cutoff point equal to the 50th percentile was defined based on the ability of KLK15 to predict progression-free survival and overall survival of the study population. RESULTS: KLK15 expression levels were significantly higher in cancerous tissues compared with benign tumors. Kaplan-Meier survival curves showed that KLK15 overexpression is a significant predictor of reduced progression-free survival (PFS; P <.001) and overall survival (OS; P <.009). Univariate and multivariate analyses indicate that KLK15 is an independent prognostic factor for PFS and OS. A weak positive correlation was found between KLK15 expression and serum CA-125 levels. CONCLUSION: KLK15 expression, as assessed by quantitative RT-PCR, is an independent marker of unfavorable prognosis for ovarian cancer.
Subject(s)
Kallikreins/genetics , Ovarian Neoplasms/genetics , Adult , Aged , CA-125 Antigen/analysis , Female , Gene Expression , Humans , Middle Aged , Prognosis , Reverse Transcriptase Polymerase Chain Reaction , Survival AnalysisABSTRACT
To study KLK14 gene expression in endocrine-related cancers, we studied its hormonal regulation in breast and ovarian cancer cell lines. Our kinetic and blocking experiments suggest that this up-regulation is mediated through the androgen receptor. We then studied the expression of KLK14 by quantitative reverse transcriptase-polymerase chain reaction in 155 consecutive ovarian tumors and correlated these findings with clinicopathologic parameters, response to chemotherapy, and survival. A stepwise reduction was observed in the levels of KLK14 messenger RNA in normal, benign, and cancerous tissues (P < .001). Expression levels were significantly higher in patients with early stage disease and optimal debulking and in patients who responded to chemotherapy. Kaplan-Meier survival curves demonstrated longer progression-free and overall survival in patients with KLK14-positive tumors than in patients with KLK14-negative tumors (P < .001). When all other prognostic variables were controlled in the multivariate analysis, KLK14 retained its prognostic significance (progression-free and overall survival, respectively, hazard ratios, 0.43 and 0.53; P = .027 and .014). A weak negative correlation was found between KLK14 expression and serum CA-125. KLK14 is a new, independent, and favorable prognostic marker for ovarian cancer.
