T-LAK Cell-Originated Protein Kinase (TOPK) as a Prognostic Factor and a Potential Therapeutic Target in Ovarian Cancer.

BACKGROUND: We aimed to clarify the clinical significance of TOPK (T-lymphokine-activated killer cell-originated protein kinase) expression in ovarian cancer and evaluate the possible effect of TOPK inhibitors, OTS514 and OTS964, on ovarian cancer cells. METHODS: TOPK expression was examined by immunohistochemistry using 163 samples with epithelial ovarian cancer (EOC). TOPK protein level and FOXM1 transcriptional level in ovarian cancer cell lines were examined by Western blot and RT-PCR, respectively. Half-maximum inhibitory concentration (IC50) values against TOPK inhibitors were examined by the MTT assay. Using the peritoneal dissemination model of ES-2 ovarian cancer cells, we examined the in vivo efficacy of OTS514. In addition, the cytotoxic effect of OTS514 and OTS964 on 31 patient-derived primary ovarian cancer cells was examined. RESULTS: TOPK was expressed very highly in 84 (52%) of 163 EOC tissues, and high TOPK expression was significantly associated with poor progression-free survival and overall survival in early-stage cases of EOC (P = 0.008 and 0.006, respectively). Both OTS514 and OTS964 showed significant growth-inhibitory effect on ovarian cancer cell lines with IC50 values of 3.0 to 46 nmol/L and 14 to 110 nmol/L, respectively. TOPK protein and transcriptional levels of FOXM1 were reduced by TOPK inhibitor treatment. Oral administration of OTS514 significantly elongated overall survival in the ES-2 abdominal dissemination xenograft model, compared with vehicle control (P < 0.001). Two drugs showed strong growth-inhibitory effect on primary ovarian cancer cells regardless of tumor sites or histological subtypes. CONCLUSIONS: Our results demonstrated the clinical significance of high TOPK expression and potential of TOPK inhibitors to treat ovarian cancer. Clin Cancer Res; 22(24); 6110-7. ©2016 AACR.

Assessment of coronary in-stent restenosis: value of subtraction coronary computed tomography angiography.

In conventional coronary computed tomography angiography (CCTA), metal artifacts are frequently observed where stents are located, making it difficult to evaluate in-stent restenosis. This study was conducted to investigate whether subtraction CCTA can improve diagnostic accuracy in the evaluation of in-stent restenosis. Subtraction CCTA was performed using 320-row CT in 398 patients with previously placed stents who were able to hold their breath for 25 s and in whom mid-diastolic prospective one-beat scanning was possible. Among these patients, 126 patients (94 men and 32 women, age 74 ± 8 years) with 370 stents who also underwent invasive coronary angiography (ICA) were selected as the subjects of this study. With ICA findings considered the gold standard, conventional CCTA was compared against subtraction CCTA to determine whether subtraction can improve diagnostic accuracy in the evaluation of in-stent restenosis. When non-assessable stents were considered to be stenotic, the diagnostic accuracy in the evaluation of in-stent restenosis was 62.7 % for conventional CCTA and 89.5 % for subtraction CCTA. When the non-assessable stents were considered to be non-stenotic the diagnostic accuracy was 90.3 % for conventional CCTA and 94.31 % for subtraction CCTA. When subtraction CCTA was used to evaluate only the 138 stents that were judged to be non-assessable by conventional CCTA, 116 of these stents were judged to be assessable, and the findings for 109 of them agreed with those obtained by ICA. Even for stents with an internal diameter of 2.5-3 mm, the lumen can be evaluated in more than 80 % of patients. Subtraction CCTA provides significantly higher diagnostic accuracy than conventional CCTA in the evaluation of in-stent restenosis.

Subtraction coronary computed tomography in patients with severe calcification.

To investigate the clinical usefulness of subtraction coronary computed tomographic angiography (CCTA) in patients with severe calcification. A 320-row area detector CT system was used in this study. The subjects were 78 patients (47 men and 31 women, 739 years of age) with an Agatston score of >300 who were able to undergo prospective one-beat scanning during a single breath-hold. The CCTA findings were compared against invasive coronary angiography. The diagnostic capabilities of CCTA for the severely calcified segments with and without the additional information provided by subtraction CCTA were compared. Severe calcification was observed in 174 (31.9%) of the 546 segments, and non-assessable regions were observed in 74 (13.6%) of the segments. The addition of subtraction CCTA information improved the diagnostic accuracy for segments with severe calcification from 67.8 to 82.8% on a per-segment basis and from 70.1 to 82.1% on a per-patient basis, with non-assessable segments considered to be stenotic. When non-assessable segments were considered to be an incorrect diagnosis, the diagnostic accuracy was improved from 48.3 to 75.9% on a per-segment basis and from 43.3 to 79.1% on a per-patient basis. In addition, when evaluation was limited to non-assessable segments, subtraction CCTA provided a diagnostic accuracy of 81.1% when non-assessable segments were considered to be stenotic or 66.2% when non-assessable segments were considered to be an incorrect diagnosis. Subtraction CCTA improves the diagnostic capabilities of CCTA in patients with severe calcification.

Analysis of blood flow in a third ventricular ependymoma and an olfactory bulb meningioma by using perfusion computed tomography.

Brain perfusion computed tomography (CT) scanning was performed in a mongrel dog and a golden retriever that were diagnosed with third ventricular tumor and olfactory bulb tumor, respectively, by contrast-enhanced CT. The tumors were pathologically diagnosed as ependymoma and meningioma, respectively. Perfusion CT results revealed that the ependymoma in this study had a lower blood flow, higher blood volume, and greater transit time of blood than the adjacent brain tissue. Further, the meningioma in this study had a higher blood flow, higher blood volume, and greater transit time of blood than the adjacent brain tissue. Perfusion CT can potentially be used for the grading of brain tumors and narrowing differential diagnosis, provided the perfusion CT data of animals are accumulated.