Motoaki Hatori

Association of the genetic polymorphism in cytochrome P450 (CYP) 1A1 with risk of familial prostate cancer in a Japanese population: a case-control study

Association between genetic polymorphisms of CYP1A1 and familial prostate cancer risk was examined by a case-control study of 185 individuals. Although the individual analysis of m1 or m2 genotype of CYP1A1 showed no significant association with prostate cancer risk, the presence of any mutated alleles significantly increased prostate cancer risk in comparison with wild-type genotypes by combination analysis (odds ratio [OR]=2.38; 95% confidence interval [CI]=1.72-3.29; P=0.0069). Furthermore, metastatic cancer had a significant association with mutated alleles of m1 and m2. These finding suggested that CYP1A1 polymorphisms has an association with prostate cancer risk, especially with progression of prostate cancer.

A novel immunosuppressive drug, FTY720, prevents the cancer progression induced by cyclosporine

Cyclosporine A (CsA), the most frequently used immunosuppressive drug, has been reported to induce cancer by a cell-autonomous mechanism. Herein, we report that FTY720, a novel immunosuppressant, prevents CsA-induced alterations in both morphology and cell motility at a low concentration (0.1 microM) and induces the CsA-treated cancer cells to undergo apoptosis at a higher concentration (more than 5 microM). The inhibitory activity of FTY720 is unrelated to the decrease of TGF-beta. We believe that a combination treatment with FTY720 and CsA not only results in a synergistic effect on allografts, but also, reduces the incidence of cancer in transplant patients.

In vivo gene transfer of hepatocyte growth factor to skeletal muscle prevents changes in rat kidneys after 5/6 nephrectomy.

Hepatocyte growth factor (HGF) has been reported to be a renal regeneration factor. We previously reported that HGF acts as a renotropic factor, inducing cell recovery from ischemic injury or drug toxicity. Gene transfer by electroporation, which uses plasmid DNA as the vector, has several advantages over the conventional gene transfer method using viral vectors, inducing the ability to perform repeated transfers without apparent immunologic responses to the DNA vector. We recently demonstrated that electroporation of the HGF gene into skeletal muscle was an effective treatment for liver injury in an animal model. We presently investigated prevention of development of chronic renal disease by repetitive HGF gene transfer in rats with 5/6 nephrectomy. Hepatocyte growth factor gene transfer‐treated rats showed better growth in body weight than untreated rats. Histologic changes such as glomerulosclerosis and interstitial fibrosis were significantly ameliorated by HGF gene transfer compared with untreated rats. Hepatocyte growth factor gene transfer by electroporation into skeletal muscle is feasible and effective against morphologic injury in subtotally nephrectomized rats.

Familial Prostate Cancer in Japan

Background:

Morphological findings in non‐episode biopsies of kidney transplant allografts treated with FK506 or cyclosporine

Abstract We conducted an analysis of biopsy specimens of non‐episode renal allografts from patients treated with tacrolimus (FK506) or cyclosporine (CsA) to evaluate chronic drug‐induced nephropathy in stable allografts. A total of 38 biopsy specimens from stable functioning renal allografts were examined. The patients had been treated with FK506 (n= 16) or CsA (n= 18) as main immunosuppressant for 0.3 to 7.4 years. Of the 38 biopsy specimens, 15 showed mild drug‐induced arteriolopathy (hyalinosis or insudative change of arterioles and small arteries) with stripeD‐form interstitial fibrosis, 10 showed minimum interstitial cellular infiltration (borderline rejection), 2 showed IgA nephropathy, 4 showed evidence of chronic rejection (transplant nephropathy) and 12 showed no abnormal findings. Of 34 renal allograft biopsy specimens with stable function, 22 (65 %) showed pathological evidence of drug‐induced nephropathy. There were no significant qualitative or quantitative differences between FK506‐ and CsA‐associated nephropathy.

Chronic expanding hematoma in the retroperitoneal space: a case report

BackgroundChronic expanding hematoma is a rare condition that develops after surgery, trauma, or injury. It can also develop at any location in the body in the absence of trauma. Clinical findings and various diagnostic imaging modalities can aid in the differential diagnosis of this condition. In general, hematomas are naturally reabsorbed and rarely cause serious problems. However, hematomas that develop slowly without a history of trauma, surgery, or bleeding disorders could be difficult to differentiate from soft tissue neoplasms. In the present case, we describe a patient, without any history or physical evidence of trauma, who exhibited a large chronic expanding hematoma in the retroperitoneal space that resulted in hydronephrosis because of the pressure exerted on the left ureter.Case presentationA 69-year-old man presented to our hospital with a swollen lesion in the left flank. A mass, 19 cm in diameter, was detected in the retroperitoneal space by computed tomography. We suspected the presence of a chronic expanding hematoma, soft tissue tumor, or left renal artery aneurysm. Surgical treatment was performed. However, postoperative histopathological examination indicated that the mass was a nonmalignant chronic expanding hematoma. No recurrence was observed during a 2-year follow-up period.ConclusionIn patients without a history of trauma who present slowly growing masses, the differential diagnosis should include chronic expanding hematoma in addition to cysts and soft tissue tumors. Moreover, the use of magnetic resonance imaging and computed tomography is essential to differentiate between chronic expanding hematoma and soft tissue tumors.

The pharmacokinetics of fosfestrol and diethylstilbestrol in chronic hemodialysis patients with prostate cancer

Abstract Background: Fosfestrol drip infusion therapy is an available endocrinotherapy for prostate cancer. But since there have been few reports of its use in chronic dialysis patients, the pharmacokinetics of fosfestrol in these patients remains unclear. We conducted fosfestrol drip infusion therapy as an induction therapy in chronic hemodialysis patients with prostate cancer.

Clinocopathological evaluation in non-episode biopsies of renal transplant allograft

Abstract Histopathological findings in renal allograft with stable function remain unclear. We therefore performed non‐episode biopsy in the long‐surviving renal allograft to investigate the histopathological changes. Our data show that, although arteriolopathy is characteristic of drug‐induced nephropathy, it is unrelated to dosage and concentration of cyclosporine or tacrolimus in non‐episode biopsy. We evaluated therefore the clinicopathological findings of arteriolopathy in this study. Non‐episode biopsy was defined as follows: as serum creatinine level lower than, 2.0 mg/dl and a urinary protein level lower than 500 mg/day. A total of 65 biopsy specimens were enrolled in this study as non‐episode biopsy. Twenty‐nine specimens revealed arteriolopathy. There were no statistically significant differences between arteriolopathy and dosage or concentration of cyclosporine or tacrolimus. Arteriolopathy in non‐episode biopsy was related to time of biopsy, kidney age, hypertension, and hyperlipidemia, suggesting that it is important for graft survival to strictly control blood pressure and blood lipid level.

The differences between late graft loss group and long‐term graft survival group in renal transplantation

Tanaka T, Takahara S, Hatori M, Toki K, Wang J‐D, Permpongkosol S, Yazawa K, Kokado Y, Oka K, Kyo M, Okuyama A, Yamanaka H. The differences between late graft loss group and long‐term graft survival group in renal transplantation. Clin Transplantation 2001: 15 (Supplement 5): 16–21. ©Munksgaard, 2001

Suicide attempt with an overdose of sunitinib

Sunitinib is an oral multi-target tyrosine kinase inhibitor approved for treating metastatic renal cell carcinoma (RCC). It is metabolized mainly by CYP3A4 to the pharmacologically active N-desethyl metabolite SU12662 [1]. In a phase I clinical trial, the recommended dose of sunitinib with manageable toxicity was determined to be 50 mg day−1 (4 weeks on, 2 weeks off; 4/2 schedule) [1]. Although a single dose of up to 350 mg was well tolerated [1], a case of sunitinib overdose has never been reported. Here, we report the pharmacokinetic analysis of sunitinib and a life-threatening adverse event in a patient with metastatic RCC who took 450 mg of sunitinib as a single dose together with brotizolam.