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ABSTRACT: p16INK4a (p16), a key molecule in bladder tumor development, inhibits the activities of cyclin-dependent kinases (CDKs) and maintains the retinoblastoma protein (pRb) in its active hypophosphorylated state. Following the finding that the p16 antitumor peptide dramatically inhibits the growth of aggressive leukemia̸lymphoma through the restoration of p16 function using the Wr-T peptide transporter system, in this study, we developed a systemic therapy using mouse‑p16 peptide (m‑p16) in subcutaneous p16‑null mouse bladder tumors. In vitro analysis showed that the growth of p16‑null bladder tumor cells and the hyperphosphorylation of their pRbs were inhibited by p16 transduction in a concentration‑dependent manner. In an animal model, p16‑null MBT‑2 cells were injected subcutaneously into KSN/SKC nude mice. The systemic delivery of the m‑p16 peptide using Wr‑T by cardiac injection significantly inhibited the growth of solid MBT‑2 tumors compared with the control phosphate‑buffered saline (PBS) injection. Histological examination by TUNEL staining revealed that apoptosis was increased and pRb phosphorylation was inhibited. Thus, the systemic peptide delivery of p16 restores the hypophosphorylation of pRb and may be a useful tool for the treatment of bladder tumors.
International Journal of Oncology 12/2012; · 2.40 Impact Factor
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ABSTRACT: OBJECTIVE: To elucidate the patterns of and risk factors for deterioration of renal function after chemotherapy in metastatic testicular cancer survivors using the estimated glomerular filtration rate. METHODS: A total of 96 patients who were treated with cisplatin-based chemotherapy for metastatic testicular cancer between January 1981 and December 2010 were enrolled in this study. The estimated glomerular filtration rate was based on the serum creatinine concentration using the formula of the Japanese Society of Nephrology. Risk factors for chronic kidney disease were examined by multivariate logistic-regression analysis. RESULTS: The median follow-up period was 70 months (range 15-342). The median pretreatment estimated glomerular filtration rate was 98 mL/min/1.73 m(2) (range 44-216), and it gradually decreased for 1 year after the end of chemotherapy, although there was no significant change in estimated glomerular filtration rate beyond 1 year. One year after chemotherapy, 22 of 96 patients (23%) showed chronic kidney disease (less than 60 mL/min/1.73 m(2) estimated glomerular filtration rate). The multivariate analysis showed that the patients with mild renal damage (estimated glomerular filtration rate 60-89 mL/min/1.73 m(2) ) and elevated blood pressure (higher than 130/80 mmHg) before treatment had a significant risk with odds ratios of 2.63 (95% confidence interval 1.09-6.73) and 4.22 (95% confidence interval 1.45-12.6), respectively. CONCLUSIONS: Close monitoring of renal function is important for at least 1 year after chemotherapy for testicular cancer, especially in patients having elevated blood pressure and/or mild renal damage before chemotherapy.
International Journal of Urology 11/2012; · 1.75 Impact Factor
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Atsushi Ikeda,
Koji Kawai,
Satoshi Ando,
Takehiro Oikawa, Hiromu Inai,
Tomokazu Kimura,
Ei-ichiro Takaoka,
Takayuki Yoshino,
Takahiro Suetomi,
Takahiro Kojima,
Jun Miyazaki,
Hiroyuki Nishiyama
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ABSTRACT: Ureteral obstruction is one of the complications of testicular tumor with retroperitoneal lymph node metastasis that requires ureteral stenting for management. We elucidated the clinical courses of ureteral obstructions and changes in renal functions in patients with indwelling ureteral stenting.
The medical records of 56 patients who were treated for metastatic testicular tumors by chemotherapy at a single institute between 2002 and 2010 were retrospectively reviewed.
Among 56 patients, 12 patients needed ureteral stenting before chemotherapy. The proportion of patients requiring ureteral stenting was significantly higher in seminoma than non-seminoma (47 and 12%, respectively, P < 0.05). The ureteral stent was removed after chemotherapy or retroperitoneal lymph node dissection in all patients, except for one patient who died of cancer during chemotherapy. At retroperitoneal lymph node dissection, ureters were spared in three patients, a partial ureterectomy was needed in one patient, and no case underwent adjunctive nephrectomy. These 11 patients presented no local and distant recurrence at median follow-up of 44 months. Ureteral stenting increased the estimated glomerular filtration rate to more than 60 ml/min before chemotherapy in all patients, but it decreased to <60 ml/min in 6 of 11 patients after chemotherapy.
Ureteral obstruction due to testicular tumor was relieved after chemotherapy or retroperitoneal lymph node dissection. Ureteral stenting was effective to improve renal function before chemotherapy, although we should pay special attention to deterioration of renal function during or after chemotherapy.
Japanese Journal of Clinical Oncology 07/2012; 42(8):748-52. · 1.78 Impact Factor
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ABSTRACT: We report a case of Kallmann syndrome in which the aging male's symptoms rating scale (AMS) was useful for assessment of subjective symptoms. A 30-year-old male was admitted to Tsukuba University Hospital with a complaint of delayed puberty in May 2003. He presented with hypogonadism, gynecomastia and anosmia. The plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone were very low. However, the LH-releasing hormone test and human chorionic gonadotropin (hCG) loading test identified normal function of pituitary and Leydig cell. After 12 months of treatment with hCG and human menopausal gonadotropin (hMG), the amount of pubic hair and the volume of testes had increased as well as the level of serum testosterone. The total score of AMS after treatment has been improved from 39 to 20 as compared with that before treatment.
Hinyokika kiyo. Acta urologica Japonica 09/2006; 52(8):661-5.
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ABSTRACT: A 37-year-old man underwent Miles' operation and adjuvant irradiation therapy for rectum cancer in 1999. The patient suffered from bilateral ureteral stricture after the previous therapies. Bilateral double-J ureteral stents were inserted and exchanged at regular intervals. Four years after the start of ureteral stenting, he complicated with gross hematuria and dysuria. When the right double-J stent was exchanged, massive bleeding from external opening of urethra was observed. Retrograde pyelography showed right uretero-iliac arterial fistula. Since endovascular treatment with covered stents had failed, we performed right common iliac artery embolization and femoral-femoral artery bypass. Two days after the operation, gross hematuria developed again. When the left ureteral stent was exchanged, active bleeding from the external meatus of urethra was revealed. Angiography showed extravasation from left common iliac artery. We diagnosed left uretero-iliac arterial fistula. Although we tried endovascular treatment with covered stent that was made of artificial vessel graft and metallic stent, thromboembolism was occurred in the covered stent. Finally, right axillo-femoral artery bypass was indicated. The last treatment achieved long-term good control of uretero-arterial fistula. The present case shows that uretero-arterial fistula is a serious complication of long-term ureteral stenting, especially in the case of post pelvic surgery and irradiation.
Nippon Hinyōkika Gakkai zasshi. The japanese journal of urology 08/2006; 97(5):752-6.
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ABSTRACT: A 22-year-old man was diagnosed with retroperitoneal seminoma associated with Klinefelter's syndrome. The tumor was 14 x 12 cm in size and surrounded the superior mesenteric artery. He received induction chemotherapy with bleomycin, etoposide and cisplatin (BEP) followed by salvage chemotherapy with paclitaxel, ifosfamide and cisplatin (TIP). The tumor considerably decreased in size and remains as a poorly defined plaque. At the time of writing, he is being followed closely and is free from progression.
International Journal of Urology 09/2005; 12(8):765-7. · 1.75 Impact Factor
