Striatal dopamine transporter density in major depression

Rationale: There are no previous data available regarding [¹²³I]β-CIT binding to the dopamine transporter sites in the basal ganglia in depressed patients. Objective: The present study tested the hypothesis that the brain DAT density in depressed patients is lower than that in matched healthy controls. Methods: Fifteen drug-naive outpatients with major depression and 18 healthy controls were investigated using single photon emission computerized tomography (SPECT) with a high-affinity dopamine transporter specific radioligand, ¹²³I-labeled β-CIT (2β-carbomethoxy-3β-(4-iodophenyl)-tropane). Results: We found a significantly higher [¹²³I]β-CIT uptake in both sides of the basal ganglia in patients with major depression than in the controls (Mann-Whitney U-test, P = 0.002 on the right and P = 0.003 on the left). Conclusions: The radioligand uptake reflecting the DAT density was significantly higher among the patients than in the controls. This finding is unexpected, since it is generally believed that monoaminergic neurotransmission is lower in depression, and therefore it could be assumed that a reduction in dopamine transmission would lead to secondary down-regulation of DAT density. However, it is possible that up-regulation of the DAT may be the primary alteration, which leads to lower intrasynaptic dopamine concentration and to lower dopamine neural transmission. Received: 20 October 1998/Final version: 25 January 1999     

Striatal dopamine transporter binding in neuroleptic-naive patients with schizophrenia studied with positron emission tomography

OBJECTIVE: Recent in vivo imaging studies indicate a dysregulated presynaptic function of the striatal dopaminergic system in patients with schizophrenia. To further explore the basis of this phenomenon, the authors studied brain dopamine transporter binding in vivo in patients with first-episode, never-medicated schizophrenia. METHOD: Nine patients with schizophrenia and nine healthy matched comparison subjects were recruited. Striatal dopamine transporter binding was measured with positron emission tomography and a specific dopamine transporter ligand, [(18)F]CFT, a radiolabeled form of 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane. RESULTS: Average caudate and putamen dopamine transporter binding potentials were almost identical in the patients and comparison subjects, but the patients lacked the right-left asymmetry of the caudate dopamine transporter binding seen in the comparison group. CONCLUSIONS: Average striatal dopamine transporter density is unaltered in neuroleptic-naive patients with schizophrenia. However, patients lack asymmetry in caudate dopamine transporter binding, which conforms with disrupted brain lateralization in this disorder.     

Diagnosis of Alzheimer's disease: MRI of the hippocampus vs delayed recall

Hippocampal volume measurements using magnetic resonance imaging (MRI) and assessment of performance in tests of delayed recall are among the most useful aids for diagnosing early Alzheimer's disease (AD) on an individual level. However, their comparative diagnostic accuracy has not been previously addressed. In this study we compared the diagnostic accuracy of these two methods in 57 patients with probable AD according to the NINCDS-ADRDA criteria, and 34 age- and gender-matched control subjects. The discriminatory power of the hippocampal volumes and delayed recall performance, Russel's Adaptation of the Visual Reproduction Test (VRT), were compared in discrimination function and receiver operator characteristic analyses. Right and left hippocampal volumes resulted in correct classification of 85.7-86.8% of the study subjects, respectively, while performance in the VRT resulted in correct classification of 93.4% of subjects. The area under curve value was 0.93 for the left hippocampus and 0.96 for the VRT. These data suggest that assessment of delayed recall with the VRT is of high diagnostic accuracy, and may surpass the diagnostic accuracy of hippocampal volumetry.     

良性肺结节HRCT的影像特征

目的：用HRCT评价良性肺结节。方法：35例经手术病理或临床治愈证实的良性肺结节行HRCT扫描，观察其CT表现。结果：18例结核瘤中15例呈圆形或椭圆形，有长、短毛刺及环蛋壳状钙化者分别为13和14例，10例周围有纤维条索影或卫星播散病灶，7例增强扫描4例呈无强化，3例呈典型的包膜样强化。9例炎性假瘤均发生在两肺上叶前段或下叶基底段，6例结节呈圆形或类圆形，边缘可见长毛刺和胸膜凹陷征，3例周边可见斑片影及血管集束征，7例增强扫描6例呈良性肺结节的动态强化。3例错构瘤2例检出结节边缘砂粒样钙化和中央脂肪密度。2例肺脓肿均表现为圆形或类圆形中央低密度结节，增强扫描呈典型的周边环状强化。1例硬化性血管瘤周围可见受压小血管。1例肺霉菌球呈不规则形，有长毛刺及多个小空腔，周围有血管集束征及胸膜凹陷征。1例纤维瘤呈圆形，边缘光滑，密度均匀。结论：常见及少见良性肺结节进行HRCT扫描有助其定性诊断。     

Interlaboratory comparison of HER-2 oncogene amplification as detected by chromogenic and fluorescence in situ hybridization.

PURPOSE: Chromogenic in situ hybridization (CISH) is a new modification of the fluorescence in situ hybridization (FISH) technique for detection of oncogene amplification in archival tumor samples. In CISH, the oncogene probe is detected using a peroxidase reaction, allowing use of transmitted light microscopy. We compared detection of HER-2/neu amplification by CISH with a Food and Drug Administration-approved two-color FISH test in an interlaboratory setting. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tumor samples from 197 breast cancers were analyzed for HER-2 amplification by CISH. Two-color FISH (PathVysion) CISH of 17 centromere was done if the observer considered it necessary to ascertain amplification status in tumors with borderline HER-2 CISH copy numbers. RESULTS: Paired CISH/FISH results were available from 192 (97%) of 197 cases, no clear difference in success rates of either method was observed. Centromere 17 CISH was considered necessary in seven tumors. CISH and two-color FISH results were concordant in 180 cases (93.8%). There were 92 and 88 tumors found HER-2 amplified and nonamplified, respectively, by both methods. Eight tumors were amplified by CISH but not by FISH, and four tumors exhibited the opposite condition (kappa coefficient 0.875). In 7 of 12 cases differences between the two methods could have related to a lack of CISH chromosome 17 information. The remaining cases were explained by difficult histology (ductal carcinoma in situ, poor representativity, dense lymphocytic infiltration, or intratumoral heterogeneity). CONCLUSIONS: These results indicate that CISH could provide an accurate and practical alternative to FISH for clinical diagnosis of HER-2/neu oncogene amplification in archival formalin-fixed breast cancer samples.     

Inactivation of cyclin D2 gene in prostate cancers by aberrant promoter methylation.

PURPOSE: Loss or abnormal expression of Cyclin D2, a crucial cell cycle-regulatory gene, has been described in human cancers; however, data for prostate tumors are lacking. We investigated the epigenetic silencing of Cyclin D2 gene in prostate cancers and correlated the data with clinicopathological features. EXPERIMENTAL DESIGN: Cyclin D2 promoter methylation was analyzed in 101 prostate cancer samples by methylation-specific PCR. In addition, we analyzed 32 nonmalignant prostate tissue samples, which included 24 samples of benign disease, benign prostatic hypertrophy, or prostatitis and 7 normal tissues adjacent to cancer. The methylation status of Cyclin D2 was correlated with the methylation of nine other tumor suppressor genes published previously from our laboratory on the same set of samples (R. Maruyama et al., Clin. Cancer Res., 8: 514-519, 2002). The methylation index was determined as a reflection of the methylated fraction of the genes examined. RESULTS: The frequency of methylation of Cyclin D2 promoter was significantly higher in prostate cancers (32%) than in nonmalignant prostate tissues (6%; P = 0.004), and it was not age related. Aberrant methylation was present at insignificant levels in peripheral blood lymphocytes (8%). We also compared methylation of cyclin D2 with methylation of nine tumor suppressor genes [published previously from our laboratory (R. Maruyama et al., Clin. Cancer Res., 8: 514-519, 2002)] studied in the same set of samples. The concordances between methylation of Cyclin D2 and the methylation of RARbeta, GSTP1, CDH13, RASSF1A, and APC were statistically significant, whereas methylation of P16, DAPK, FHIT, and CDH1 were not significant. The differences in methylation index between malignant and nonmalignant tissues for all 10 genes were statistically significant (P < 0.0001). Among clinicopathological correlations, the high Gleason score group had significantly greater methylation frequency of Cyclin D2 (42%; P = 0.004). Although the high preoperative serum prostate-specific antigen (PSA) group did not have significantly greater methylation frequency, methylation of Cyclin D2 had higher mean PSA value. Also, the prostate cancers in the high Gleason score group had high mean values of PSA. CONCLUSIONS: Our results indicate that methylation of Cyclin D2 in prostate cancers correlates with clinicopathological features of poor prognosis. These findings are of biological and potential clinical importance.     

Monounsaturated fatty acids in serum triacylglycerols are associated with response to neoadjuvant chemotherapy in breast cancer patients

Changes in cellular lipid metabolism are a common feature in most solid tumors, which occur already in early stages of the tumor progression. However, it remains unclear if the tumor‐specific lipid changes can be detected at the level of systemic lipid metabolism. The objective of this study was to perform comprehensive analysis of lipids in breast cancer patient serum samples. Lipidomic profiling using an established analytical platform was performed in two cohorts of breast cancer patients receiving neoadjuvant chemotherapy. The analyses were performed for 142 patients before and after neoadjuvant chemotherapy, and the results before chemotherapy were validated in an independent cohort of 194 patients. The analyses revealed that in general the tumor characteristics are not reflected in the serum samples. However, there was an association of specific triacylglycerols (TGs) in patients' response to chemotherapy. These TGs containing mainly oleic acid (C18:1) were found in lower levels in those patients showing pathologic complete response before receiving chemotherapy. Some of these TGs were also associated with estrogen receptor status and overall or disease‐free survival of the patients. The results suggest that the altered serum levels of oleic acid in breast cancer patients are associated with their response to chemotherapy.     

Autocrine TNFalpha signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis

A small-molecule mimetic of Smac/Diablo that specifically counters the apoptosis-inhibiting activity of IAP proteins has been shown to enhance apoptosis induced by cell surface death receptors as well as chemotherapeutic drugs. Survey of a panel of 50 human non-small-cell lung cancer cell lines has revealed, surprisingly, that roughly one-quarter of these lines are sensitive to the treatment of Smac mimetic alone, suggesting that an apoptotic signal has been turned on in these cells and is held in check by IAP proteins. This signal has now been identified as the autocrine-secreted cytokine tumor necrosis factor alpha (TNFalpha). In response to autocrine TNFalpha signaling, the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis.