Prompted by the findings of previous studies with positron emission tomography and single photon emission computed tomography, which demonstrated hypoperfusion or hyperperfusion in the left temporal lobe in isolated patients with transient global amnesia (TGA), we compared the sensitivity of diffusion-weighted (DW) magnetic resonance imaging (MRI) with that of conventional T1- and T2-weighted MRI in patients with TGA. Ten patients with the typical syndrome of a pure TGA were included in the study. For all patients, a coronal DW sequence, a steady-state free precession (SSFP) sequence, and conventional T1- and T2-weighted turbo spin-echo sequences were obtained. Seven of the 10 patients had elevated signal intensity in the left hippocampal region on DW MRI; moreover, 3 of these 7 patients exhibited bilateral signal abnormality in this sequence. All conventional T1- and T2-weighted images as well as all follow-up studies were normal. The signal elevation in DW MRI correlates with a decrease in the interstitial space and with cellular edema in the temporal lobe during TGA. The underlying pathomechanism causing this cellular edema cannot be clearly outlined using DW MRI. Our data are, however, compatible with spreading depression. This is the first study to show that DW MRI is a sensitive MRI method for evaluating TGA, especially in the early stage of the disease.

Previous studies have found that treatment with lithium over a 4-week period may increase the concentration of N-acetyl-aspartate (NAA) in both bipolar patients and controls. In view of other findings indicating that NAA concentrations may be a good marker for neuronal viability and/or functioning, it has been further suggested that some of the long term benefits of lithium may therefore be due to actions to improve these neuronal properties. The aim of the present study was to utilize H magnetic resonance spectroscopy ( H MRS) to further examine the effects of both lithium and sodium valproate upon NAA concentrations in treated euthymic bipolar patients. In the first part of the study, healthy controls (n =18) were compared with euthymic bipolar patients (type I and type II) who were taking either lithium (n =14) or sodium valproate (n =11), and NAA : creatine ratios were determined. In the second part, we examined a separate group of euthymic bipolar disorder patients taking sodium valproate (n =9) and compared these to age- and sex-matched healthy controls (n =11), and we quantified the exact concentrations of NAA using an external solution. The results from the first part of the study showed that bipolar patients chronically treated with lithium had a significant increase in NAA concentrations but, in contrast, there were no significant increases in the sodium valproate-treated patients compared to controls. The second part of the study also found no effects of sodium valproate on NAA concentrations. These findings are the first to compare NAA concentrations in euthymic bipolar patients being treated with lithium or sodium valproate. The results support suggestions that longer-term administration of lithium to bipolar patients may increase NAA concentrations. However, the study suggests that chronic administration of sodium valproate to patients does not lead to similar changes in NAA concentrations. These findings suggest that sodium valproate and lithium may not share a common mechanism of action in bipolar disorder involving neurotrophic or neuroprotective effects.

Inhibitors of the bromodomain and extraterminal domain (BET) protein family attenuate the proliferation of several tumor cell lines. These effects are mediated, at least in part, through repression of c-MYC. In colorectal cancer, overexpression of c-MYC due to hyperactive WNT/b-catenin/TCF signaling is a key driver of tumor progression; however, effective strategies to target this oncogene remain elusive. Here, we investigated the effect of

The elucidation of molecular events that confer tamoxifen resistance to estrogen receptor α (ER) positive breast cancer is of major scientific and therapeutic importance. Here, we report that LEM4 overexpression renders ER+ breast cancer cells resistant to tamoxifen by activating the cyclin D-CDK4/6 axis and the ERα signaling. We show that LEM4 overexpression accelerates tumor growth. Interaction with LEM4 stabilizes CDK4 and Rb, promotes Rb phosphorylation and the G1/S phase transition. LEM4 depletion or combined tamoxifen and PD0332991 treatment significantly reverses tamoxifen resistance. Furthermore, LEM4 interacts with and stabilizes both Aurora-A and ERα, promotes Aurora-A mediated phosphorylation of ERα-Ser167, leading to increase in ERα DNA-binding and transactivation activity. Elevated levels of LEM4 correlates with poorer relapse-free survival in patients with ER+ breast cancer undergoing endocrine therapy. Thus, LEM4 represents a prognostic marker and an attractive target for breast cancer therapeutics. Functional antagonism of LEM4 could overcome tamoxifen resistance.

Approximately 30% of pediatric patients with ALCL relapse. While brentuximab vendotin has demonstrated excellent activity in ALCL, it has not been used for newly diagnosed patients. Children's Oncology Group trial ANHL12P1 determined the toxicity and efficacy of brentuximab vedotin with chemotherapy in children with newly diagnosed, non-localized, ALK+/CD30+ ALCL. From 2013 to 2017, 68 children with ALK+ ALCL were enrolled and received brentuximab vedotin (Arm BV). All patients received five-day prophase followed by six cycles of chemotherapy at 21-day intervals. Brentuximab vedotin was given on day 1 of each of the six cycles. Of the 67 eligible patients for toxicity evaluation, 66 completed all six cycles of chemotherapy resulting in 399 cycles evaluable. There were no toxic deaths, no cases of progressive multifocal leukoencephalopathy syndrome, and no cases of grade 3 or 4 neuropathy. The two-year EFS is 79.1% (95% CI, 67.2% to 87.1%). The two-year OS is 97.0% (95% CI, 88.1% to 99.2%). Fourteen patients relapsed and were the only events contributing to EFS. 11 of 14 (79%) relapses occurred within ten months of initial diagnosis, with only one patient (1.5%) having relapsed during therapy. Quantitative RT-PCR for NPM-ALK at baseline (minimal disseminated disease) demonstrated prognostic value and impacted 2-year EFS (P=0.0004). Overall, the addition of brentuximab vedotin to standard chemotherapy does not add significant toxicity, nor does it alter the desired interval between cycles. The addition of brentuximab vedotin prevented relapses during therapy and the overall and event-free survival estimates compare favorably with results obtained using conventional chemotherapy.

These findings examine two key components of the PI-cycle in treated euthymic bipolar (myo-inositol and PME concentrations). The results from this study are consistent with the suggestion that chronic treatment with either lithium or sodium valproate in bipolar patients may normalize PI-cycle functioning.

The purpose of this study was to evaluate the utility of magnetic resonance (MR) relative cerebral blood volume (rCBV) maps for studying regional hemodynamic changes in interictal and ictal epilepsy patients. Ten epilepsy patients were examined on a 1.5 T MR system. Nine patients were investigated interictally and one patient ictally. In the nine interictal patients, the dynamic plane was defined coronally through the hippocampus symmetrically. For the ictal patient, an axial dynamic plane was defined and the patient was scanned during seizure. Positron emission tomography (PET) studies were performed in 8 of the 10 patients. Lower rCBV of the left hippocampus was predicted by rCBV maps in seven of the nine interictal patients. The mean ratios of rCBV were 1.96 for left hippocampus/white matter and 2.49 for right hippocampus/ white matter. The difference between these two ratios is statistically significant (P = 0.01, t‐test). In two of the nine interictal temporal lobe epilepsy patients, lower rCBV areas were observed in the right hippocampus. In the ictal patient, the regional rCBV map demonstrated increased blood volume in the lesions. In eight of eight patients who underwent PET studies, MR rCBV findings were consistent with PET findings. The results show that regional hemodynamic changes in epilepsy can be evaluated with dynamic contrast‐enhanced MR imaging. MR rCBV maps are sensitive to characterize seizure foci both ictally and interictally.J. Magn. Reson. Imaging 1999; 9:435–440. © 1999 Wiley‐Liss, Inc.

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