Interferon-α-based immunotherapy in metastatic renal cell carcinoma patients with the primary tumor in situ.

OBJECTIVE: We reviewed the outcomes of metastatic renal cell carcinoma patients with the primary tumor in situ who initially underwent interferon-α-based immunotherapy to evaluate the effect of this therapy on metastatic sites as well as primary kidney tumor and survival. METHODS: Thirty-one patients, for whom upfront cytoreductive nephrectomy was considered to be inappropriate because of poor performance status and far-advanced disease, were the subject of the present study. Tumor response and reduction in the size of metastatic sites and primary kidney tumor were assessed. Overall survival distributions were estimated using the Kaplan-Meier method with the significance determined using the log-rank test. RESULTS: Partial response was observed in 11 patients, yielding an overall response rate of 35%. Seventeen patients had regression or stabilization of metastatic sites, while progression of metastatic sites was observed in the remaining 14 patients. Regarding the maximum response of primary kidney tumor, a reduction in kidney primary tumor size was observed in 42% of the patients and the mean reduction rate in these patients was 18.2% (range: 3-36%). Furthermore, the reduction in the size of metastatic sites was significantly associated with that in the size of primary kidney tumor (R(2)= 0.432, P< 0.0001). The median survival for the 31 patients was 17 months. The median survival was 42 months in patients with regression or stabilization of metastatic sites and 7 months in those without (P< 0.001). CONCLUSIONS: The present study suggests that metastatic sites as well as primary kidney tumor respond to interferon-α-based immunotherapy in metastatic renal cell carcinoma patients with primary tumor in situ.

[Relationship between dose of mycophenolate mofetil and the occurrence of cytomegalovirus infection and diarrhea in renal transplant recipients].

To establish guidelines for avoiding the side effects of mycophenolate mofetil (MMF) in renal transplant recipients with tacrolimus (TAC)-based immunosuppression, the relationship between the daily dose of MMF and the occurrence of side effects was analyzed in this study. The frequency of side effects was investigated retrospectively in 28 renal transplant recipients treated with immunosuppression (men 14 : women 14, age: 33.0+/-12.4 years, weight: 50.9+/-10.7 kg). Cytomegalovirus (CMV) infection and diarrhea were the most frequent side effects in the early transplant phase (from transplantation to 3-month biopsy) in the recipients. In 18 recipients, excluding the recipients with risk factors for CMV infection (ABO-incompatible transplantation, donor (+)/recipient (-) CMV serostatus, etc.), no significant correlation was shown between the daily dose of MMF and the occurrence of CMV infection in the two-sample t-test. On the other hand, the daily dose in the diarrhea group (33.2+/-4.3 mg/kg/day, n = 5) was significantly higher than that in the no-diarrhea group at 30 days (28.4+/-3.7 mg/kg/day, n = 23, p < 0.05) and 90 days (25.7+/-4.4 mg/kg/day, n = 21, p < 0.005) after transplantation, respectively. The receiver-operating characteristic (ROC) curve also revealed that the risk of diarrhea increased with a daily MMF dose higher than 30 mg/kg/day. In conclusion, to decrease the risk of diarrhea in the early transplant phase in renal transplant recipients with TAC-based immunosuppression, the daily dose of MMF should not be more than 30 mg/kg/day.

In vitro model of suicide gene therapy for alpha-fetoprotein-producing gastric cancer.

BACKGROUND: Gastric adenocarcinoma producing alpha-fetoprotein (AFP) has a very poor prognosis. In search of new therapeutic strategies against AFP-producing gastric cancer, we examined the efficacy of suicide gene therapy, which has been effective on AFP-producing hepatoma. MATERIALS AND METHODS: The herpes simplex virus thymidine kinase (HSVtk) gene was transduced into an AFP-producing gastric adenocarcinoma cell line, FU97, using adenovirus vectors carrying the constructed AFP enhancer/promoter element, followed by ganciclovir (GCV) administration. RESULTS: Expression of the transgene was evident in FU97 but not in an AFP-nonproducing gastric adenocarcinoma cell line, MKN28, which meant that AFP enhancer/promoter-specific transcriptional targeting was achieved by the vectors. The viability of FU97 but not of MKN28 significantly decreased after the suicide gene therapy in vitro. CONCLUSION: Therapeutic application of the AFP enhancer/promoter-specific transfer of the HSVtk gene followed by GCV administration against AFP-producing gastric cancer deserves attention and further research.

Expression of matrix metalloproteinase in the fluids of renal cystic lesions.

PURPOSE: Cystic lesions of the kidney are common conditions usually diagnosed by imaging. Although simple cysts are easy to diagnose, preoperative diagnosis of a complicated cystic lesion can be difficult. There is little information available on the biological activity of cystic fluid and associations with clinicopathological findings. We analyzed the expression of matrix metalloproteinase (MMP) in the fluids of benign and malignant renal cystic lesions to clarify matriolytic activities in the cyst. MATERIALS AND METHODS: Included in this study were 22 samples of cystic fluids from renal cystic lesions, including 14 benign cysts and 8 cystic renal cell carcinomas. MMP-2 and 9 was determined in fluids using gelatin zymography and enzyme-linked immunosorbent assay. RESULTS: MMP-2 expression was ubiquitously observed on zymography except for 2 benign cysts associated with acquired cystic disease of the kidney. MMP-9 was detected in 7 of 8 carcinomas but in only 2 of 14 benign cysts (p <0.01). The concentration of MMP-2 and 9 was significantly higher in cystic carcinomas than in benign cysts (p <0.01). CONCLUSIONS: Our data show that MMPs were detectable in cystic fluids in the presence of renal cystic changes. MMP-2 and 9 are more abundant in cystic carcinoma fluids than in benign cystic fluids. These observations suggest that matriolytic enzymes in renal cystic fluid reflect biological aggressiveness and in part explain the pathogenesis of renal cystic lesions.