Akiyoshi Katagiri

E-cadherin expression in renal cell cancer and its significance in metastasis and survival

Decreased expression of E-cadherin (E-CD), a homotypic intercellular adhesion molecule, is considered to elicit detachment of tumour cells from primary lesions, which is the first stage of metastasis. Since renal cell cancer (RCC) shows a relatively high frequency of metastasis, we focused our interest on E-CD expression in RCC and its clinicopathological implications. We examined E-CD expression in normal kidney and RCC by immunohistochemical staining. In normal kidney, E-CD expression was localised in distal tubules and collecting ducts. In RCC, 20 of 106 primary lesions (18.9%) expressed E-CD, whereas none showed positive staining for eight metastatic lesions. There was a statistically significant correlation between loss of E-CD expression and advanced stages of RCC. Kaplan-Meier analysis showed better prognosis in the group with preserved E-CD expression than without E-CD expression (Cox-Mantel test, P = 0.022, the average follow-up was 32 months or until death). This study suggests that the patients with decreased E-CD expression may be associated with metastasis, resulting in poor prognosis. However, frequency of E-CD expression in RCC is lower than in other cancers, which may be derived from the localised distribution of E-CD expression in normal kidney.

Significance of Serum Amyloid A on the Prognosis in Patients with Renal Cell Carcinoma

Evidence of systemic inflammation, i.e., elevation of serum C–reactive protein, interleukin‐6, and/or the erythrocyte sedimentation rate, is correlated to poorer prognosis of patients with renal cell carcinoma (RCC). Serum amyloid A (SAA) has been recognized mainly as acute‐phase reactant.

Loss of human E-cadherin (ECD) correlated with invasiveness of transitional cell cancer in the renal pelvis, ureter and urinary bladder

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 normo-expression, 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 alpha-catenin mRNA in RT4 and HT1376, and only alpha-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.

Immunohistochemical detection of P-glycoprotein and GSTP1-1 in testis cancer.

P-glycoprotein (Pgp) and pi-class glutathione S-transferase (GSTP1-1) are thought to be correlated with multiple drug resistance. In immunohistochemical staining, non-seminomatous germ cell tumours, which are more refractory than seminomas to anti-cancer chemotherapy, frequently expressed Pgp and GSTP1-1. Western blot analysis demonstrated lower amount of GSTP1-1 in seminoma than in teratoma. These results suggest that Pgp and GSTP1-1 might contribute to drug resistance in testis cancers.

Significance of serum-soluble CD95 (Fas/APO-1) on prognosis in renal cell cancer patients

SummarySerum-soluble CD95 (sCD95) levels for 72 renal cell cancer patients were significantly higher than those of 17 healthy donors. Twenty-one of 72 patients had elevated (defined as more than mean of healthy donors + 2 s.d.) sCD95. The disease-specific survival rate was significantly lower in the elevated sCD95 group. Serum sCD95 level was shown to be an independent prognostic factor by univariate and multivariate analysis, indicating a possible significant role in determining treatment strategies.

Adoptive Immunotherapy of Patients with Metastatic Renal Cell Cancer Using Lymphokine-Activated Killer Cells, lnterleukin-2 and Cyclophosphamide: Long-Term Results

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).

Expression of E-Cadherin and Catenins on Testis Tumor

E-cadherin (ECD) is a homophilic Ca2+-dependent adhesion molecule associated with cell-to-cell interactions and normal growth. Recent reports have suggested that decrease or loss of ECD facilitates tumor progression and/or metastasis. ECD functions in a complex called an adherens junction, which includes several other proteins including α- and β-catenin. In the present study, fresh-frozen sections from 32 testis cancers, 16 seminomas and 16 non-seminomatous germ cell tumors (NSGCT), were examined immunohistochemically. E-cadherin was not expressed on normal germ cells, but expressed on 3 (18.8%) of 16 seminomas and 10 (62.5%) of 16 NSGCTs, mainly on the epithelial component of teratoma cells. α-Catenin was detected on 0 (0%) of 13 seminomas and 4 (25%) of 16 NSGCTs. β-Catenin was detected on 10 (71.4%) of 14 seminomas and 13 (81.2%) of 16 NSGCTs. ECD was detected significantly more frequently on NSGCTs than on seminomas. Immunoblot analysis confirmed the expression of ECD and β-catenin in NSGCTs. Expression of ECD and catenins may reflect the degree of differentiation and provide some information on the character of the tumor.

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

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 microgram/ml increased susceptibility to LAK cells. Presence of 5FU at 2 micrograms/ml but not at 0.2 microgram/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.

Obstruction of the ileal ureter by mesenteric vessels occurring 5 years after total ureteral substitution for bilateral ureteral stenosis due to systemic lupus erythematosus

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.

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

We have shown previously that interferon (IFN)-alpha 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-alpha pretreatment also affects the sensitivity of ACHN cells to lysis by NK cells or IFN-alpha-activated NK cells. A 51Cr-release cytotoxicity assay demonstrated that pretreatment of ACHN with IFN-alpha decreased their susceptibility to NK cells and IFN-alpha-activated NK cells in a dose-dependent manner. Moreover, to investigate the usefulness of 5-fluorouracil (5FU) for combination with IFN-alpha therapy, we examined the effect of preincubation with 5FU on the susceptibility of ACHN. IFN-alpha-induced protection of ACHN from lysis by IFN-alpha-activated NK cells weakened in the presence of 5FU at 0.2 microgram/ml. An adhesion assay showed that preincubation of ACHN with 5FU and IFN-alpha did not alter the adhesion of IFN-alpha-activated NK cells. A cold target competition analysis did not show any difference between untreated and 5FU and/or IFN-alpha-treated competitors. These results suggest that one of the mechanisms of 5FU for combination with IFN-alpha therapy might depend on changes of RCC cells in intrinsic lysability involving a post-binding stage of the lytic cycle to NK cells.