Cancer stem-like cells of ovarian clear cell carcinoma are enriched in the ALDH-high population associated with an accelerated scavenging system in reactive oxygen species.

OBJECTIVE: In ovarian cancer cases, recurrence after chemotherapy is frequently observed, suggesting the involvement of ovarian cancer stem-like cells (CSCs). The chemoresistance of ovarian clear cell carcinomas is particularly strong in comparison to other epithelial ovarian cancer subtypes. We investigated the relationship between a CSC marker, aldehyde dehydrogenase 1 (ALDH1), and clinical prognosis using ovarian clear cell carcinoma tissue samples. Furthermore, we investigated the antioxidant mechanism by which CSCs maintain a lower reactive oxygen species (ROS) level, which provides protection from chemotherapeutic agents. METHODS: Immunohistochemical staining was performed to examine the CSC markers (CD133, CD44, ALDH1) using ovarian clear cell carcinoma tissue samples (n=81). Clear cell carcinoma cell lines (KOC-7C, OVTOKO) are separated into the ALDH-high and ALDH-low populations by ALDEFLUOR assay and fluorescence-activated cell sorting (FACS). We compared the intracellular ROS level, mRNA level of the antioxidant enzymes and Nrf2 expression of the two populations. RESULTS: High ALDH1 expression levels are related to advanced stage in clear cell carcinoma cases. ALDH1 expression significantly reduced progression free survival. Other markers are not related to clinical stage and prognosis. ALDH-high cells contained a lower ROS level than ALDH-low cells. Antioxidant enzymes were upregulated in ALDH-high cells. ALDH-high cells showed increased expression of Nrf2, a key transcriptional factor of the antioxidant system. CONCLUSIONS: ALDH-positive CSCs might have increased Nrf2-induced antioxidant scavengers, which lower ROS level relevant to chemoresistance in ovarian clear cell carcinoma.

[The intrarenal distribution of prostaglandin E2 and thromboxane A2 in the rat with unilateral ureteral obstruction or unilateral nephrectomy].

BACKGROUND: We evaluated the intrarenal distribution of prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) on the rats that underwent unilateral ureteral obstruction (UUO), unilateral nephrectomy (UNX) or sham operation. METHODS: Male Sprague-Dawley rats were divided into three groups; left ureteral obstruction (UUO), left nephrectomy (UNX) and sham-operation (Control). They were sacrificed at 1, 3, 6, 12, 24 hours and Day 2, Day 3, Day 5, Day 7 and Day 9 after surgery. Intrarenal distribution of eicosanoids were immunohistochemically detected on both kidneys of UUO rats, and on right kidneys of UNX and Control rats. RESULTS: PGE2: In the obstructed kidneys, immunostained PGE2 increased in medullary interstitium at one hour to 6 hours, and in glomeruli and cortical interstitium at 6 hours. An increase of immunostained PGE2 was observed again in cortical interstitium at Day 3 to 5, and in medullary interstitium at Day 2 to 5. In the intact opposite kidneys, expression of immunostained PGE2 increased in glomeruli at Day 5 to 7, and in medullary interstitium at Day 3 to 5. In UNX, immunostained PGE2 increased in the medullary interstitium of the remnant kidneys at 3 hours and Day 3 to 7. On the other hand, an increase of immunostained PGE2 observed in glomeruli and cortical interstitium of these kidneys at Day 5 to 7. TxB2: In the obstructed kidneys, immunostained TxB2 increased in glomeruli and cortical interstitium at 6 hours, and in medullary interstitium at 3 to 12 hours. Predominant expression of TxB2 was observed in medullary interstitium at 3 hours compared to PGE2. We also observed an increase of immunostained TxB2 in cortical interstitium at Day 3 to 5, and in medullary interstitium at Day 2 to 5. In the intact opposite kidneys, immunostained TxB2 increased in medullary interstitium at 3 hours and Day 3. In the remnant kidneys of UNX, an increase of immunostained TxB2 was demonstrated in glomeruli at 6 hours and Day 7, and in medullary interstitium at 3 to 6 hours and Day 3 to 7. CONCLUSION: In the obstructed kidneys, imbalance between PGE2 and TxA2 may contribute to the progression of renal injuries. The fact that expression patterns of these eicosanoids in the opposite kidneys of UUO different from that of the remnant kidneys of UNK, even though both were similarly associated with functional loss of contralateral kidneys, suggested that the opposite kidneys of UUO were affected by any additional factors different from that responsible for the remnant kidneys of UNK.

Unicalyceal kidney associated with ureteral anomalies.

A unicalyceal kidney is a very rare anomaly of the urinary system. We report 4 cases of unicalyceal kidneys in infants. All cases were associated with ureteral anomalies: megaureter on the involved side, and/or ectopic ureter with vesicoureteral reflux or renal agenesis on the contralateral side. In order to preserve renal function we recommend surgical treatment for patients with unicalyceal kidney when they have ureteral anomalies.

[Renal function of contralateral kidney after total or partial removal of kidney with ectopic ureter].

The effects of partial or total removal of the kidney with ectopic ureter on the contralateral kidney were evaluated using DMSA renal uptake rate on 8 patients. After partial nephrectomy on 6 cases, the affected residual kidneys showed significant decrease in DMSA renal uptake rate in 2 cases in which the extirpated kidneys had normal renal tissue in part but did not show significant change in DMSA uptake rate in 4 cases in which the extirpated kidneys were dominated mainly with dysplasia. Post-operative increase in DMSA uptake rate of the contralateral kidneys were significant in 3 of 4 patients who had the operation before they became 2 years old. In 2 of these 3 cases, pre-operative scintigram showed extremely low rate of DMSA renal uptake. Four cases aged 2 years old and over did not show post-operative increase in the uptake rate. As we have previously reported on the cases with hydronephrosis, these results suggest that 1) existence of obstruction caused by ectopic ureter inhibit the development of the contralateral kidney and 2) the growth of the kidney can resume the release of that obstruction, if the release is made while the kidneys are still in developing stage.

[Evaluation of renal function and prediction of renal functional recovery in children with unilateral hydronephrosis using renal pelvic urine].

In 29 children with unilateral hydronephrosis who underwent surgery at the age from 2 months to 15 years (27 patients with ureteropelvic junction stenosis and 2 with obstructive megaureter), beta 2-microglobulin (beta 2-MG), alpha 1-microglobulin (alpha 1-MG), N-acetyl-beta-D-glucosaminidase (NAG) and albumin were determined in renal pelvic urine from the hydronephrotic kidney to evaluate renal dysfunction accompanying urinary tract obstruction. Moreover, it was also examined whether it is possible to predict functional recovery of the hydronephrotic kidney on the basis of relation between these indices and pre- and postoperative changes in renal dimercaptosuccinic acid (DMSA) uptake rate. The values of beta 2-MG, alpha 1-MG, NAG and albumin in urine from the renal pelvis were high in 48%, 50%, 75% and 83% of the patients, respectively. Among the patients of one year and up, those with low preoperative DMSA uptake rate tended to have high values of beta 2-MG, alpha 1-MG and NAG. On the contrary, albumin level was high in 78% of patients who had good preoperative DMSA uptake rate. With respect to the relation between pre- and postoperative changes in DMSA uptake rate and each index, beta 2-MG and alpha 1-MG were high in 73% and 62% of patients who exhibited a marked increase in postoperative DMSA uptake rate. In patients without a remarkable change in DMSA uptake rate before and after surgery, on the other hand, the values of these were high only in 25% and 36%.(ABSTRACT TRUNCATED AT 250 WORDS)

[Enoxacin concentration in human prostatic tissue after 3-day administration].

The penetration of enoxacin into prostatic tissue was examined Thirty-five patients with benign prostatic hypertrophy entered the study. Enoxacin was administered orally in a dose of 200 mg three times daily for 3 days preoperatively. Blood samples were taken simultaneously at the time of tissue sampling. The patients were divided into groups 1 and 2. In group 1, tissue sampling was done after about 17 hours of final administration of the drug. The mean concentration of enoxacin in prostatic tissue was 1.87 +/- 1.23 micrograms/g and 1.05 +/- 0.458 micrograms/ml in serum. In group 2, sampling was done after 5.5 hours of final administration. The mean concentration of enoxacin in prostatic tissue was 2.51 +/- 0.725 micrograms/g and 1.78 +/- 0.586 micrograms/ml in serum.