[A case of an advanced gastric cancer patient on hemodialysis achieving long-term progression-free survival after CPT-11+CDDP therapy].

A 59-year-old male with chronic kidney disease was diagnosed as having advanced gastric cancer(cT2N1P0H1M0), and CPT-11+CDDP therapy was started for him simultaneously with hemodialysis(HD). Serum CDDP concentrations were measured in the 1st course, and free-platinum(f-Pt)showing the anti-tumor effect was found to be eliminated by HD. Serum f-Pt levels, however, re-elevated until 24 hours after HD completion. Serum concentrations measured in the 15th course showed that f-Pt levels became higher than those observed in the 1st course, suggesting that CDDP was not completely removed by HD. Medical treatment was continued until the liver metastases were judged to be a progression disease at completion of the 18th course. When CDDP was administered to patients on HD, it was necessary to pay attention to various CDDP serum concentrations, and to tailor the dose to a tolerable level in each patient. Such an individual therapy might enable CPT-11+CDDP therapy to be one of the medical treatments of choice for advanced gastric cancer patients on HD.

Activation of signal transducer and activator of transcription 3 correlates with cell proliferation and renal injury in human glomerulonephritis.

BACKGROUND: Signal transducer and activator of transcription (STAT) 3 plays an important role in the regulation of cell proliferation. However, the mechanism of STAT3 activation in human glomerulonephritis is unclear. METHODS: STAT3 activation was determined using immunohistochemistry for phosphorylated STAT3 (p-STAT3) in normal human kidney and various types of glomerulonephritis. We also identified the cell exhibiting activated p-STAT3 expression in human glomerulonephritis and correlated STAT3 activation with renal function and histologic injury. RESULTS: p-STAT3 staining was identified in glomeruli and some tubules in normal human kidney. p-STAT3 positive glomerular cells were significantly increased in lupus nephritis, IgA nephropathy and vasculitis compared with normal kidney. p-STAT3 positive tubulointerstitial cells were significantly increased in IgA nephropathy and vasculitis compared with normal kidney. Glomerular and tubulointerstitial p-STAT3 staining was significantly decreased after steroid therapy. There was a significant correlation between the number of p-STAT3 positive cells and the number of PCNA positive glomerular and tubulointerstitial cells in all cases of glomerulonephritis. Furthermore, renal function inversely correlated with the number of p-STAT3 positive glomerular and tubulointerstitial cells in all cases of glomerulonephritis. CONCLUSIONS: The present study has identified STAT3 activation in normal human kidney and a marked increase in STAT3 activation in many forms of glomerulonephritis. The correlation of STAT3 activation with clinical and histologic parameters suggests that this pathway plays an important role in the pathogenesis of kidney disease. Furthermore, localization of STAT3 activation to individual cell types suggests that this pathway may play a pivotal role in promoting renal inflammation and fibrosis.

Simple surgical treatment for pleuroperitoneal communication without interruption of continuous ambulatory peritoneal dialysis.

Pleuroperitoneal communication is a complication of continuous ambulatory peritoneal dialysis (CAPD) that can necessitate cessation of CAPD. Hemodialysis was started on a 52-year-old woman and shifted to CAPD 1 month later. However, 18 days after initiation of CAPD, her chest radiograph showed a right-side hydrothorax. Thoracentesis yielded a colorless pleural effusion with markedly higher glucose levels than in her serum, indicating the presence of pleuroperitoneal communication. Three days later, thoracoscopic surgery was performed. A colored dialysis solution preoperatively injected into the abdominal cavity identified intraoperatively leakage from the diaphragm. The leakage points were closed by a no-knife-type automatic stapler with absorbable polyglycolic acid felt and fibrin glue. CAPD was restarted on the operative day, and there was no recurrence of the right hydrothorax. We conclude that this simple method can be used effectively to treat pleuroperitoneal communication.

Signal transducer and activator of transcription 3 involvement in the development of renal interstitial fibrosis after unilateral ureteral obstruction.

BACKGROUND: In vitro studies suggest that the signal transducer and activator of transcription (STAT) plays a critical role in renal fibrosis. However, the process of STAT activation in vivo remains unclear. This study in rats aimed to localize STAT3 activation within the kidney and examine the in vivo relationship between STAT3 activation and renal fibrosis. METHODS: Unilateral ureteral obstruction (UUO) was induced in the rats and the kidneys examined 3 or 7 days after obstruction. Activation of STAT3 in western blot and immunohistochemical analyses was identified by the phosphorylated form of STAT3 (pSTAT3). RESULTS: Myofibroblasts were identified by alpha-smooth muscle actin expression and were upregulated in obstructed kidneys. pSTAT3 was localized mainly in tubular epithelial cells of collecting ducts in normal and obstructed kidneys and interstitial cells in obstructed kidneys. After UUO, western blotting showed a fourfold increase in pSTAT3, with a peak at day 7. Immunostaining showed a sixfold increase in pSTAT3 at day 7 in tubular epithelial cells and a 2500-fold increase at day 7 in interstitial cells. CONCLUSION: STAT3 was activated in rat tubular epithelial cells and myofibroblasts after UUO, suggesting that STAT3 may contribute to the progression of interstitial fibrosis.

Effect of lactate and bicarbonate on human peritoneal mesothelial cells, fibroblasts and vascular endothelial cells, and the role of basic fibroblast growth factor.

BACKGROUND: In patients on long-term continuous ambulatory peritoneal dialysis (CAPD), peritoneal dysfunction may occur due to loss of peritoneal mesothelial cells, peritoneal fibrosis and neovascularization. Lactate, long used as a buffer in peritoneal dialysates, has been substituted by bicarbonate in recent years. However, their effects on the peritoneum of CAPD patients are unknown. This study investigated the influence of lactate and bicarbonate on peritoneal dysfunction in CAPD patients. METHODS: The mitochondrial activity of human peritoneal mesothelial cells (HPMCs) and their expression of basic fibroblast growth factor (bFGF) were studied after culture under various conditions. We also assessed the mitochondrial-activating effect of the supernatant of those cultures on human peritoneal fibroblasts (HPFBs) and human umbilical vein endothelial cells (HUVECs) and the effect of recombinant human bFGF on the mitochondrial activity of HPFBs and HUVECs. We used the WST-1 assay to determine mitochondrial activity in HPMC. RESULTS: At pH 7.4, the mitochondrial activity of HPMCs was lowest in a medium containing 40 mM (Lac), intermediate in a lactate (15 mM) plus bicarbonate (25 mM) medium (Lac/Bic), and highest in a 40 mM bicarbonate medium (Bic). In culture supernatant, the increase of bFGF was: Lac > Lac/Bic > Bic. Mitochondrial activation of HPFBs and HUVECs was stimulated by HPMC culture supernatants in the following decreasing order: Lac > Lac/Bic > Bic. The effects of these supernatants were suppressed by a bFGF-neutralizing antibody, while recombinant bFGF caused concentration-dependent mitochondrial activation in HPFBs and HUVECs. CONCLUSIONS: The role of bFGF in peritoneal fibrosis and neovascularization may be important. A bicarbonate-containing medium is better than a lactate-containing medium for preserving cell viability in HPMCs and preventing bFGF expression by these cells.

Viability of, and basic fibroblast growth factor secretion by, human peritoneal mesothelial cells cultured with various components of peritoneal dialysis fluid.

In patients on long-term continuous ambulatory peritoneal dialysis (CAPD), peritoneal dysfunction is considered to be due to the loss of peritoneal mesothelial cells and to subsequent peritoneal fibrosis and neovascularization. Our aim in the present study was to clarify the role of various components of peritoneal dialysis fluid in the occurrence of peritoneal dysfunction in CAPD patients. We used a cell counting assay and ELISA to study the viability of human peritoneal mesothelial cells and their secretion of basic fibroblast growth factor (bFGF)--which induces peritoneal fibrosis and neovascularization--by cells cultured with various components of peritoneal dialysis fluid. The viability of cultured cells, ranked from highest to lowest by solution type, was bicarbonate (40 mEq/L) > lactate (15 mEq/L) + bicarbonate (25 mEq/L) > lactate (40 mEq/L). Viability also showed a concentration-dependent decrease in the presence of advanced glycation end-products of bovine serum albumin. The bFGF level in the supernatant showed a concentration-dependent increase in the presence of glucose and glycated albumin; bFGF level decreased as the bicarbonate concentration increased. Low levels of glucose, lactate, and glycated albumin, and a high concentration of bicarbonate may preserve the viability of peritoneal mesothelial cells and prevent bFGF secretion.