Tamoxifen inhibits the proliferation of non­melanoma skin cancer cells by increasing intracellular calcium concentration.

Tamoxifen is an estrogen receptor (ER) antagonist used as first-line chemotherapy in breast cancer. Recent studies suggest that tamoxifen may be effective not only for ER­positive but also for ER­negative cancer cases. The aim of the present study was to investigate the antiproliferative effect of tamoxifen against human non­melanoma skin cancer cells. Tamoxifen inhibited the proliferation of the skin squamous cell carcinoma (SCC) cell lines A431, DJM­1 and HSC­1. A431 cells did not express ER­α or -ß, suggesting that tamoxifen may exert antiproliferative effects on skin SCC cells via a non­ER­mediated pathway. Tamoxifen increased the intracellular calcium concentration of skin SCC cells, and this increase in intracellular calcium concentration by calcium ionophore A23187 suppressed the proliferation of skin SCC cells. These data indicate that tamoxifen inhibited the proliferation of human skin SCC cells via increasing intracellular calcium concentration. Voltage-gated calcium channels and non­selective cation channels are involved in the increase in intracellular calcium concentration induced by tamoxifen. The broad-spectrum protein kinase C (PKC) inhibitor phloretin significantly attenuated the antiproliferative effect of tamoxifen on skin SCC cells. From these data, it may be concluded that tamoxifen inhibits the proliferation of skin SCC cells by induction of extracellular calcium influx via calcium channels in the plasma membrane and by subsequent activation of PKC.

Significance of the renal functional reserve in reflux nephropathy: an evaluation according to the degree of glomerular damage.

OBJECTIVE: In the treatment of progressive reflux nephropathy (RN), the therapeutic benefit and prognosis of the renal function in RN patients appears to be influenced by the degree of renal functional reserve. We designed this study to determine the presence and characteristics of the renal functional reserve in RN patients. MATERIALS AND METHODS: In the 35 RN patients with renal scars (19 males; mean age 16.1 years), an exogenous renal clearance test was performed to measure the glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF). In the second half of this test, the renal functional reserve was estimated by measuring the GFR and ERPF during low-dose dopamine infusion. These measurements were then compared with the glomerular size, which had been previously determined by a renal biopsy. RESULTS: Among the patients with a normal glomerular size (-2SD to +2SD), the GFR markedly increased after low-dose dopamine infusion (from 112.15 +/- 52.51 to 182.07 +/- 69.95 mL/min, p < 0.0001), whereas an increase in ERPF was not significant. Among the patients with an enlarged glomerular size (+2SD to +4SD), the GFR and ERPF increased significantly over the baseline values (from 54.60 +/- 32.90 to 114.00 +/- 65.48 mL/min, p = 0.0076; from 281.01 +/- 152.54 to 622.43 +/- 392.73 mL/min, p = 0.0155, respectively). Among the patients with an extremely enlarged glomerular size (>+4SD), both the GFR and ERPF remained almost completely unchanged. CONCLUSION: The renal functional reserve was present even among progressive RN patients with a glomerular size ranging between +2SD and +4SD.

Prognostic significance of the number of renal glomeruli in reflux nephropathy.

OBJECTIVE: To monitor the decrease in the number of glomeruli in reflux nephropathy (RN) and to investigate its association with glomerular hypertrophy or clinical data, as some cases of RN progress to end-stage renal failure, although the mechanism of progression remains unknown and is generally thought to depend on remnant normal renal tissue mass, i.e. the number of remnant renal glomeruli (functional nephrons). PATIENTS AND METHODS: From 1987 onward, a renal biopsy was taken in 71 patients (mean age 8.08 years) in two institutions to estimate the prognosis of patients with RN. RESULTS: The number of glomeruli per unit area and glomerular size in grossly normal renal tissue specimens were determined to explore the potential association between these variables and the total renal scars, renal function (glomerular filtration rate, GFR), or daily urinary protein excretion. The number of glomeruli was closely correlated with the actual size of glomeruli (y = 14.783 - 0.052x, R = 0.782). To a lesser extent, the number of glomeruli was also closely correlated with the size of glomeruli expressed in sds (y = 6.264 - 0.832x, R = 0.630). There was a good correlation between the number of glomeruli and the extent of renal scarring, renal function, or daily urinary protein excretion, although its association with renal function (GFR) was least evident. CONCLUSION: There was an association between the decrease in the number of glomeruli and glomerular hypertrophy, decreased renal function, or increased proteinuria. A renal biopsy taken from radiographically and macroscopically normal regions can be useful for assessing RN, and the size and number of glomeruli in the specimens might provide an important measure for estimating the prognosis of RN.

Expression of gap junction protein connexin32 in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

BACKGROUND: The gap junction (GJ) plays important roles in the maintenance of tissue homeostasis, the control of cell growth and differentiation, and the prevention of experimental hepatocarcinogenesis. In this study, we examined the relationship between the expression of the GJ protein connexin (Cx) 32 in 24 human hepatocellular carcinomas (HCCs) and 29 non-carcinomatous liver specimens (NCLs) of 31 patients. METHODS: An immunohistochemical study of Cx32 was done in 24 HCCs and 29 NCLs from 31 patients who had undergone hepatic resection. RESULTS: The Cx32 expression decreased gradually as the disease progressed to cirrhosis and HCC. In all Cx32 positive HCCs, the expression was mostly recognized in cytoplasm, not only on the cell membrane. This internalization of Cx32 was also recognized in liver specimens showing hepatitis and cirrhosis, although it was less frequent than in the HCCs. CONCLUSIONS: These findings suggest the possibility that changes in both the amount and the distribution of Cx32 may be implicated in human hepatocarcinogenesis.

[Three cases report on the epispadiac urethral duplication in male].

A case of complete type and two cases of incomplete type of epispadiac urethral duplication are reported. In the complete one, the accessory urethra (14 cm in length) opened 1.5 cm proximal to the dorsum of the penis. In two cases of incomplete type, the epispadiac openings located at the base of the penis or higher. The sinuses were lined with transitional epithelium proximally, and with squamous cells on the distal half of the accessory urethra, which suggests a developmental origin. We conclude that these sinuses may etiologically represent the identical origin without regard to complete type or incomplete type.

Sequential changes of connexin32 and connexin26 in ischemia-reperfusion of the liver in rats.

Serial changes in expression of hepatic gap junction components, connexin32 and connexin26 expressions during ischemia (60 min)-reperfusion injury of the liver were evaluated by immunofluorescence staining and reverse transcription-polymerase chain reaction in rats. Hepatic tissue calcium content and liver enzymes (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase), were also examined. Connexin expressions were down-regulated during ischemia and steeply increased during the early reperfusion period. This upsurge in connexin was coincided with the augmentation in tissue calcium content level. And the mRNA levels of connexin changed in parallel with the connexin protein level until 60 min after reperfusion. Since it is known that the changes in intracellular Ca(2+) concentration controls the intercellular communication via gap junction, these findings suggest the possibility that gap junction may play a definitive role in reperfusion injury of the liver. Further studies may be necessary to clarify the exact role of connexins in hepatic ischemia-reperfusion injury.