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The chromosomal passenger complex (CPC) plays a pivotal role in controlling accurate chromosome segregation and cytokinesis during cell division. Aurora-B, one of the chromosomal passenger proteins, is important for the mitotic spindle assembly checkpoint (SAC). Previous reports noted that Aurora-C is predominantly expressed in male germ cells and has the same subcellular localization as Aurora-B. Increasing evidence indicates that Aurora-C is overexpressed in many somatic cancers, although its function is uncertain. Our previous study showed that the aberrant expression of Aurora-C increases the tumorigenicity of cancer cells. Here, we demonstrate that overexpressed Aurora-C displaces the centromeric localization of CPCs, including INCENP, survivin, and Aurora-B. When cells were treated with nocodazole to turn on SAC, both the Aurora-B protein stability and kinase activity were affected by overexpressed Aurora-C. As a result, the activation of spindle checkpoint protein, BubR1, and phosphorylation of histone H3 and MCAK were also eliminated in Aurora-C-overexpressing cells. Thus, our results suggest that aberrantly expressed Aurora-C in somatic cancer cells may impair SAC by displacing the centromeric localization of CPCs.

AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection. METHODS: A total of 143 patients (83.1% of the 172 participants in the phase II study) participated in the follow-up study. Of these patients, 50 had received no treatment, 48 had received 160 mg/d PI-88, and 45 had received 250 mg/d PI-88 during the phase II trial. Safety parameters and the following efficacy endpoints were investigated: (1) time to recurrence; (2) disease-free survival; and (3) overall survival. RESULTS: PI-88 at 160 mg/d delayed the onset and frequency of HCC recurrence, and provided a clinically significant survival advantage for up to 3 years after treatment compared with those of the control group: (1) the recurrence-free rate increased from 50% to 63%, and (2) time to recurrence at the 36th percentile was postponed by 78%. The efficacy of administering PI-88 at 250 mg/d was confounded by a high dropout rate (11 out of 54 patients). Additionally, subgroup analyses of patients with (1) multiple tumors or a single tumor ≥ 2 cm; and (2) hepatitis B or C revealed that administering PI-88 at 160 mg/d conferred the most significant survival advantage (56.8% improvement in disease-free survival, P = 0.045) for patients with both risk factors for recurrence. CONCLUSION: Administering PI-88 at 160 mg/d is a safe and well-tolerated dosage that may confer significant clinical benefits for patients with HCC.

According to the coupling effect between two adjacent waveguides, we propose a new optoelectronic device of filtering undesired wavelengths. The structure, composed of many parallel waveguides, was analyzed by the finite difference beam propagation method employing the Runge-Kutta method (RKBPM). Our simulation shows that the narrow bandwidth of the filter is achieved by increasing the total number of the waveguides.

Hepatocellular carcinoma (HCC), the 5th most frequent cancer worldwide, has a 5-year survival rate of 14% because it is difficult to diagnose early. The goal of this project is to construct a panel of circulation-derived DNA markers to use in a urine test for the early detection of HCC to improve its prognosis. The HCC-specific p53 codon 249T mutation was the first candidate DNA marker used to explore the criteria needed to detect HCC-derived DNA markers in urine of patients with HCC in a sensitive, noninvasive manner. We showed previously that urine contains circulation-derived DNA fragments that are mostly fewer than 300 bp, designated as low-molecular-weight (LMW) urine DNA. The LMW urine DNA contains DNA from tumor tissues when tumors are present. The tumor-derived DNA fragments offer the potential to develop absolutely noninvasive urine tests for the detection of any cancer with known DNA biomarkers. A locked nucleic acid clamp-mediated PCR assay for the p53 249T mutation, targeting only 41 nucleotides of the template, followed by melting curve analysis, was developed and tested using patient urine samples. Total urine DNA samples from 17 patients with HCC were fractionated into high-molecular-weight (HMW) (>1 kb, mostly cell-associated) DNA from the urinary tract and LMW (< 1 kb, mostly circulation derived) DNA and subjected to the p53 249T mutation assay. Encouragingly, samples from 9 of 17 patients with HCC contained detectable p53 249T mutation in the LMW urine DNA fraction and only 1 of 17 matching HMW urine DNA fraction samples was found to contain p53 249T mutated DNA. These findings suggest that the assay target template size of 41bp is suitable to detect HCC-derived DNA markers in urine and that the p53 249T mutation detected in LMW urine DNA is derived from the circulation. Next, we tested a larger number of samples of LMW urine DNA from patients with HCC. Overall, we detected the p53 249T mutation in 50.8% of the LMW urine DNA samples from patients with HCC (60/118). Of the 49 subjects whose urine was positive for the p53 mutation before surgery, the p53 mutation was no longer detectable in the urine of 29 of those patients after surgical removal of the tumor. This result suggested that the p53 249T mutations detected in the urine before surgery were derived from the surgically removed HCC. For controls, we tested LMW urine DNA from patients with hepatitis and cirrhosis and from normal subjects or patients with colorectal cancer and found that 0 of 32 normal (0%), 0 of 31 colorectal cancer (0%), 7 of 69 hepatitis (10.1%), and 6 of 47cirrhosis (12.8%) samples contained detectable amounts of p53 249T mutated DNA. A urine test that includes multiple DNA markers for HCC screening and recurrence monitoring is currently being explored. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 715. doi:1538-7445.AM2012-715

e14673 Background: Ampulla of vater cancer (AVC) is a rare malignancy. Limited data are available regarding the efficacy of systemic chemotherapy in patients with recurrent or metastatic AVC. Infus...

Background/Purpose: Laparoscopic donor nephrectomy (LDN) has emerged as the preferred technique worldwide, and has contributed to a dramatic increase in living kidney donation during the past decade. We adopted LDN in 2002 with the intention of increasing living kidney donation incentive and maintaining equivalent donor/recipient outcome. Methods: Forty-five LDNs were performed between September 2002 and November 2007. Donor demographics, operative characteristics, perioperative complications and donor/recipient outcome were reviewed retrospectively. The LDN series was divided into earlier and later groups for comparison. To confirm the safety and efficacy of LDN, we compared the results with those of previous series and our open donor nephrectomy (ODN) series. Results: All 45 LDN kidneys were procured and transplanted successfully. Mean donor operation time was 327.7±10.2 minutes, blood loss was 286.0±48.3 mL, and warm ischemia time was 233.9±19.6 seconds. Two (4.4%) open conversions happened in the earlier group. There was a significant decrease in warm ischemia time and donor intraoperative complications in the later group. There was no donor mortality and there were no repeat surgical procedures. Delayed graft function occurred in 8.9% of cases and three (6.7%) recipients developed ureteral complications. All but one recipient was discharged with adequate renal function. Graft function continued in 41 of the 43 harvested kidneys (95.3%). Compared with ODN, there was a significant decrease in donor postoperative stay in the LDN series (p = 0.00). There was no difference between the series with regard to donor safety, donor outcome, and immediate and long-term recipient outcome. Conclusion: The number of living kidney donations increased significantly after adopting LDN in our series. The equivalent donor/recipient outcome of the LDN series compared with that of previous and ODN series was achieved with increasing experience.

A 43-year-old woman with liver cirrhosis and hepatocellular carcinoma was admitted for the chief problem of ascites. Laboratory data revealed a leukocyte count of 3.8 × 10 9 /L on the second day of admission. Spironolactone was prescribed for diuresis beginning on the third day. Routine blood tests on the tenth day disclosed marked leukopenia (1.8 × 10 9 /L). Four days later, the leukocyte count was still 1.8 × 10 9 /L and a differential count revealed agranulocytosis (neutrophils, 0.25 × 10 9 /L). Eight days after withdrawal of spironolactone, the leukocyte count returned to normal (leukocytes, 4.9 × 10 9 /L; neutrophils, 1.76 × 10 9 /L). On review of the patient's clinical condition, concurrent medication, and previous reports, we highly suspected that this episode of agranulocytosis was caused by spironolactone. Unlike four previously reported cases, this one did not involve furosemide, which is reported to be associated with leukopenia and agranulocytosis.