Patients with Advanced Ovarian Cancer Administered Oral Etoposide following Taxane as Maintenance Chemotherapy.

INTRODUCTION: The concept of maintenance therapy is one of the highly relevant approaches in the management of advanced ovarian cancer. The fundamental goal of maintenance therapy is to improve survival outcomes. We attempted to reinforce maintenance chemotherapy by adding oral etoposide following taxane administration. CASES: We retrospectively evaluated 14 patients with advanced ovarian cancer who had achieved clinically defined complete response to a primary platinum/taxane chemotherapy regimen and who were administered oral etoposide (50 mg/day × 21 days per cycle monthly for 3-5 cycles) following paclitaxel or docetaxel administration as maintenance chemotherapy. With regard to oral etoposide toxicity, grade 2 oral mucositis and grade 3 anemia were observed in 1 patient each. Three to five cycles of etoposide were administered to all patients, though daily dosage was reduced to 25 mg in 2 patients due to toxicity. The median progression-free survival was 43.5 months, the median overall survival was 86 months, and 5-year overall survival was 77.1%. CONCLUSION: The results from this ovarian cancer treatment evaluation suggest that oral etoposide may be administered safely following paclitaxel or docetaxel as maintenance chemotherapy. We expect this regimen to contribute to the improvement in the survival outcomes of patients with advanced ovarian cancer.

Colonic distention at screening CT colonography: role of spasmolytic agents and body habitus.

Sufficient colonic dilation is important when using CT colonography (CTC) for colorectal cancer screening. We investigated the effect of antispasmodic agents and the patient body habitus on the degree of colonic dilation in screening CTC.We assessed the effect of clinical characteristics [age, gender, body mass index (BMI), and the presence of diverticula] and the use of antispasmodics on colonic distention in 140 patients who underwent CTC for colorectal cancer screening. The CTC was performed in both the supine- and prone positions. Seventy patients received antispasmodics prior to CT examination and the other 70 did not. Colonic distention was scored using a 5-point scale: 1=collapsed, 2=poorly visualized, 3=visualized but underdistended, 4=acceptable, and 5=excellent. Images scored as 4 or 5 were considered to be of diagnostic quality. The mean visual evaluation score was significantly higher in the supine- than the prone position (4.2±0.5 vs. 4.0±0.5, p<0.01). For the supine position, only the use of antispasmodic was statistically associated with sufficient colonic dilation by univariate logistic analysis (odds ratio=2.365, p=0.03). For the prone position, age, BMI, and the use of antispasmodic were statistically associated with sufficient colonic dilation by multivariate analysis. The odds ratio of these parameters was 0.955 (p=0.02), 0.874 (p=0.03), and 2.391 (p=0.02), respectively.We obtained sufficient colonic dilation with an antispasmodic for CTC in both positions. Younger age and a lower BMI were also associated with better colonic dilation in the prone position.

Detection of flat colorectal polyps at screening CT colonography in comparison with conventional polypoid lesions.

BACKGROUND: Although the screening of small, flat polyps is clinically important, the role of CT colonography (CTC) screening in their detection has not been thoroughly investigated. PURPOSE: To evaluate the detection capability and usefulness of CTC in the screening of flat and polypoid lesions by comparing CTC with optic colonoscopy findings as the gold standard. MATERIAL AND METHODS: We evaluated the CTC detection capability for flat colorectal polyps with a flat surface and a height not exceeding 3 mm (n = 42) by comparing to conventional polypoid lesions (n = 418) according to the polyp diameter. Four types of reconstruction images including multiplanar reconstruction, volume rendering, virtual gross pathology, and virtual endoscopic images were used for visual analysis. We compared the abilities of the four reconstructions for polyp visualization. RESULTS: Detection sensitivity for flat polyps was 31.3%, 44.4%, and 87.5% for lesions measuring 2-3 mm, 4-5 mm, and ≥6 mm, respectively; the corresponding sensitivity for polypoid lesions was 47.6%, 79.0%, and 91.7%. The overall sensitivity for flat lesions (47.6%) was significantly lower than polypoid lesions (64.1%). Virtual endoscopic imaging showed best visualization among the four reconstructions. Colon cancers were detected in eight patients by optic colonoscopy, and CTC detected colon cancers in all eight patients. CONCLUSION: CTC using 64-row multidetector CT is useful for colon cancer screening to detect colorectal polyps while the detection of small, flat lesions is still challenging.

Quantitative proteomic analysis to discover potential diagnostic markers and therapeutic targets in human renal cell carcinoma.

Renal cell carcinoma (RCC) is relatively resistant to chemotherapy and radiotherapy. Recent advances in drug development are providing novel agents for the treatment of RCC, but the effects are still minimal. In addition, there is an urgent need to identify diagnostic markers for RCC. In this report, to discover potential diagnostic markers and therapeutic targets, we subjected RCC samples to a quantitative proteomic analysis utilizing 2-nitrobenzenesulfenyl (NBS) reagent. Proteins were extracted from RCC and adjacent normal tissue, obtained surgically from patients, and labeled with NBS reagent containing six (12)C or (13)C. This was followed by trypsin digestion and the enrichment of labeled peptides. Samples were then subjected to analysis by MALDI-TOF MS. NBS-labeled peptides with a 6 Da difference were identified by MS/MS. Thirty-four proteins were upregulated in more than 60% of the patients of which some were previously known, and some were novel. The identity of a few proteins was confirmed by Western blotting and quantitative real time RT-PCR. The results suggest that NBS-based quantitative proteomic analysis is useful for discovering diagnostic markers and therapeutic targets for RCC.

Knock-down of sorcin induces up-regulation of MDR1 in HeLa cells.

In our previous study, the MDR1/Pglycoprotein-overexpressing multidrug resistant subline, Hvr100-6, was established from the human cervical carcinoma cell line HeLa-Ohio (HeLa) by stepwise exposure to an anti-microtubule agent, vinblastine sulfate, a typical substrate of MDR1. Their gene and protein expression profiles were analyzed herein, and 148 genes were identified to be differentially expressed by cDNA microarray analysis. The up-regulation of sorcin, a soluble resistance-related calcium-binding protein of 22 kDa, was confirmed in Hvr100-6 cells by the proteome analysis. To clarify the relationship between MDR1 and sorcin, HeLa cells were treated with small interfering RNAs (siRNAs) targeted for theirs mRNAs. The siRNA for MDR1 mRNA resulted in its decrease by 86% and 61% on the days 1 and 2 after the treatment, whereas the expression level of sorcin mRNA was not changed. On the other hand, the siRNA for sorcin mRNA suppressed its expression by 80-90% on days 1-3 after the treatment. Interestingly; suppression of sorcin induced a more than 3-fold increase in the expression level for MDR1 mRNA. An efflux function of MDR1 evaluated with using rhodamine 123 as a probe showed a tendency to be increased in HeLa cells treated with siRNA for sorcin, compared with that in the cells treated with scramble siRNA. The activity and the expression of caspase-3 in the sorcin knock-down HeLa cells were relatively higher than those in the cells treated with scramble siRNA. Thus, we demonstrated that sorcin might be a partial suppressor of MDR1 expression. Furthermore, the present study suggested that sorcin repressed apoptosis via dysfunction of caspase-3.

Loss of spinal substance P pain transmission under the condition of LPA1 receptor-mediated neuropathic pain.

Among various machineries occurring in the experimental neuropathic pain model, there exists the loss of pain transmission through C-fiber neurons as well as the hypersensitivity through A-fibers. The current study reveals that molecular machineries underlying the latter hypersensitivity are derived from the events through LPA1 receptor and its downstream RhoA-activation following peripheral nerve injury. The loss of C-fiber responses, which are mediated by spinal substance P (SP) pain transmission was observed with the nociceptive flexor responses by intraplantar injection of SP in nerve-injured mice. The immunohistochemistry revealed that SP signal in the dorsal horn was markedly reduced in such mice. All these changes were completely abolished in LPA1-/- mice or by the pretreatment with BoNT/C3, a RhoA inhibitor. In addition, the loss of C-fiber responses and the down-regulation of spinal SP signal induced by single intrathecal LPA injection were also abolished in such treatments. All these results suggest that the loss of pain transmission through polymodal C-fiber neurons is also mediated by the LPA1 activation following nerve injury.