Publications (6)3.49 Total impact
Article: Adoptive Immunotherapy of Patients with Metastatic Renal Cell Cancer Using Lymphokine‐Activated Killer Cells, lnterleukin‐2 and Cyclophosphamide: Long‐Term Results[show abstract] [hide abstract]
ABSTRACT: Background Initial results of adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) appeared to offer promise for treating renal cell cancer (RCC). However, lower response rates were seen in subsequent trials, and the long-term results of this treatment method have not been fully reported. In this study, we examine long-term results of adoptive immunotherapy using LAK cells, IL-2, and cyclophosphamide (LAK/IL-2/CPM therapy).Methods We administered 10 courses of therapy to 9 patients with advanced RCC. One patient had liver and para-aortic lymph node metastases; the others had only lung metastases. The clinical effects were initially evaluated 4 weeks after therapy and follow-up was continued for periods of 43 to 76 months.Results The 4-week evaluation revealed 3 complete responses (CR), 3 partial responses (PR), 1 minor response (MR), 1 patient with no change in disease status (NC), and 2 patients whose disease progressed (PD). One CR patient remained apparently free of disease for 43 months. After tumors recurred in the lung of another CR patient further disease progression was suppressed by IL-2 administration until the patient died from other causes at 46 months. The third CR patient showed tumor recurrence in the lung and was re-treated with the sameLAK/CPM/IL-2 therapy. Lung tumors decreased in size (PR), but the patient died due to brain metastasis 2 months after the second round of treatment. The 2 initial PR patients, as well as the MR and NC patients, developed regrowth or new metastatic lesions within 2 to 15 months following therapy. The 2 PD patients died 2 and 9 months after therapy.Conclusion Long-term effects ofLAK/IL-2/CPM therapy were not correlated with the maximal response observed 4 weeks after therapy. AlthoughLAK/IL-2/CPM therapy appears suitable for use as induction therapy in RCC, our data suggest that long-term suppression will require surgical removal of remnant tumors or more intensive maintenance therapy.International Journal of Urology 06/2007; 5(1):16 - 21. · 1.75 Impact Factor
Article: Obstruction of the ileal ureter by mesenteric vessels occurring 5 years after total ureteral substitution for bilateral ureteral stenosis due to systemic lupus erythematosus.[show abstract] [hide abstract]
ABSTRACT: We previously reported a case of bilateral ureteral stenosis accompanied by systemic lupus erythematosus, which was successfully managed by total ureteral reconstruction using a segment of the ileum. Herein, we describe an unusual complication in the same patient, which we experienced 5 years after the ileal-ureteral substitution. Left-sided back pain repeated together with transient obstruction of the ileal ureter interposed between the right and left renal pelvis. Consequently, exploratory laparotomy revealed that left colic vessels oppressed and caused obstruction, and the obstructed ileal ureter was released by reconstitution of these vessels instead of re-anastomosis of the ileal ureter. Left hydronephrosis and related back pain disappeared postoperatively. The number of patients with an indication of ileal-ureteral substitution is increasing for various disorders, and thus, the present report gives additional suggestions for the follow up of patients with ileal ureter.International Journal of Urology 02/2006; 13(1):80-3. · 1.75 Impact Factor
Article: [Intermittent oral hormonal chemotherapy using estramustine phosphate and etoposide for the treatment of hormone-refractory prostate cancer].[show abstract] [hide abstract]
ABSTRACT: Seventeen patients were given lower dose and intermittent oral administration of estramustine phosphate (6 mg/kg/day) and etoposide (30 mg/m2/day) for 7 days. Then administration was discontinued for 7 days. This administration cycle was repeated. Therapy was continued until evidence of disease progression or unacceptable toxicity occurred. Fifteen of the 17 patients were finally evaluated for PSA response. Overall, the pretreatment PSA levels were lowered at least 50% from baseline in 7 (47%) of the 15 patients. The median survival was 65 weeks. Five of the 17 patients complained of anorexia or nausea during the treatment, but none of them showed over grade 2 anorexia, none requiring transfusion or hospitalization. None of the patients showed edema, deep venous thrombosis, thrombocytopenia, anemia or myocardial infarction. Because of its rare and mild adverse effects, this intermittent administration of oral estramustine and oral etoposide may be a useful and secure regimen for hormone refractory prostate cancer.Hinyokika kiyo. Acta urologica Japonica 01/2004; 49(12):709-14.
Article: 5-Fluorouracil increases susceptibility of renal cell cancer cell lines to lymphokine-activated killer cells: evidence for alteration not at the level of recognition but at a post-binding stage of the lytic cycle[show abstract] [hide abstract]
ABSTRACT: To investigate the usefulness of 5-Fluorouracil (5FU) for combination with immunotherapy, we examined the effect of preincubation with 5FU on the susceptibility of a renal cell cancer (RCC) cell line, ACHN, to lymphokine-activated killer (LAK) cells. A 4-h 51Cr release assay showed a remarkable increase in the susceptibility of ACHN cells to LAK cells. Dose response experiments demonstrated that 5FU at concentrations as low as 0.002 μg/ml increased susceptibility to LAK cells. Presence of 5FU at 2 μ/ml but not at 0.2 μg/ml in media blocked LAK activity induction by IL-2. Furthermore, an adhesion assay showed that preincubation with 5FU did not alter the adhesion of LAK cells to tumor cells nor the expression of intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-3 (LFA-3) or major histocompatibility complex (MHC) class I molecules on tumor cells. Cold target competition did not show any difference between 5FU-treated and untreated competitors. These results suggest that increased susceptibility of RCC cells to LAK cells due to preincubation with 5FU might depend on changes in intrinsic lysability involving a post-binding stage of the lytic cycle.Cancer Letters.
Article: Loss of human E-cadherin (ECD) correlated with invasiveness of transitional cell cancer in the renal pelvis, ureter and urinary bladder[show abstract] [hide abstract]
ABSTRACT: Loss or decreased expression of E-cadherin (ECD), which forms an epithelial junction complex that includes several other proteins and triggers signal transduction, may contribute to tumor progression. In the present study, we examined 90 transitional cell cancers (TCCs), 47 urinary bladder cancers and 43 ureteral or renal pelvic cancers, as well as TCC and papilloma cell lines to determine whether they express ECD. We classified ECD expression into normo-expression (like normal epithelial), decreased and loss of ECD staining on TCCs (urinary bladder, renal pelvic or ureteral). We found that low-stage TCCs expressed normal ECD in 68%, decreased of ECD in 20% and loss of ECD in 12%, whereas high-stage TCCs expressed 29%, 41% and 30% of ECD staining, respectively (P < 0.01). Furthermore, grade 1 TCCs were all estimated to show normoexpression, grade 2 TCCs expressed normal ECD in 49%, decreased of ECD in 41% and loss of ECD in 10% grade 3 TCCs classified as 20%, 30% and 50%, respectively (P < 0.01). Staining for cultured cell lines showed positive membranous staining for ECD in a benign papilloma cell line, RT4 and a TCC cell line, HT1376, but not in a TCC cell line, T24. Reverse-transcription polymerase chain reaction showed the presence of ECD and α-catenin mRNA in RT4 and HT1376, and only α-catenin in T24. Thus, it is more likely -that decrease or loss of ECD might contribute to the malignant character of tumor cells and result in tumor progression.Cancer Letters.
Article: Interferon-α-induced protection of renal cell cancer cell line from lysis by natural killer cells and increase of susceptibility by treatment with 5-fluorouracil[show abstract] [hide abstract]
ABSTRACT: We have shown previously that interferon (IFN)-α reduces the sensitivity of renal cell cancer (RCC) cell lines ACHN and KRC/Y to lysis by lymphokine-activated killer (LAK) cells. The close relationship between natural killer (NK) cells and LAK cells prompted us to investigate whether IFN-α pretreatment also affects the sensitivity of ACHN cells to lysis by NK cells or IFN-α-activated NK cells. A 51Cr-release cytotoxicity assay demonstrated that pretreatment of ACHN with IFN-α decreased their susceptibility to NK cells and IFN-α-activated NK cells in a dose-dependent manner. Moreover, to investigate the usefulness of 5-fluorouracil (5FU) for combination with IFN-α therapy, we examined the effect of preincubation with 5FU on the susceptibility of ACHN. IFN-α-induced protection of ACHN from lysis by IFN-α-activated NK cells weakened in the presence of 5FU at 0.2μg/ml. An adhesion assay showed that preincubation of ACHN with 5FU and IFN-α did not alter the adhesion of IFN-α-activated NK cells. A cold target competition analysis did not show any difference between untreated and 5FU and/or IFN-α-treated competitors. These results suggest that one of the mechanisms of 5FU for combination with IFN-α therapy might depend on changes of RCC cells in intrinsic lysability involving a post-binding stage of the lytic cycle to NK cells.Cancer Letters.