[The diagnostic value of pre-biopsy magnetic resonance imaging for precise detection of clinically localized prostate cancer compared to post-biopsy setting].

A total of 136 patients who underwent radical prostatectomy following histological diagnosis of prostate cancer by transrectal biopsy and 3-Tesla magnetic resonance imaging (MRI) were evaluated. MRI was performed on 26 patients before prostate biopsy (pre-biopsy group) and on 110 patients after prostate biopsy (post-biopsy group). We defined the largest tumor focus in a radical prostatectomy specimen as the index cancer. We compared the accuracy of MRI in detecting and localizing the index cancer in the groups. The sensitivity of detecting the index cancer by MRI was significantly (p = 0.012) higher in the pre-biopsy group (96.2%) than in the post-biopsy group (77. 3%). The negative predictive value of extracapsular invasion was 84.6% in the pre-biopsy group and 80.7% in the post-biopsy group. The average interval between biopsy and MRI was 42.8 days. Artifacts due to post-biopsy hemorrhage were observed in 32 (29.1%) of the patients in the post-biopsy group. The sensitivity of detecting the index cancer by MRI was significantly (p = 0.022) higher in 78 patients without artifacts due to hemorrhage (83.3%) than in the 32 patients with artifacts due to hemorrhage (62.5%). Even if MRI is delayed until after prostate biopsy,the artifact due to hemorrhage markedly interferes with the accuracy of MRI. Although pre-biopsy MRI is more accurate than post-biopsy MRI,there are some problems to be solved,such as cost effectiveness and the detectability of low-malignant and small cancers.

[Causes and salvage of failed urethroplasties for traumatic urethral injury].

OBJECTIVES: Salvage urethroplasty after failed repair of traumatic urethral injury is a urological challenge, and we herein describe our experience with it. METHODS: From October 2010 to January 2012, five patients underwent salvage repair of failed urethroplasties for traumatic urethral injuries: three bulbar straddle injuries and two pelvic fracture urethral injuries. One of the three failed urethroplasties for bulbar straddle injuries was a stricture excision and primary anastomosis, and its failure was due to periurethral abscess formation. Another was an augmented anastomotic urethroplasty using buccal mucosa, and its failure was due to periurethral abscess formation. The third was a tube graft urethroplasty using buccal mucosa, and its failure was due to a stricture at the anastomotic site. Two failed urethroplasties for pelvic fracture urethral injuries were perineal anastomotic repairs combined with corporal separation and inferior pubectomy, and the failures of both were due to ischemic bulbar necrosis. The urethral gap lengths estimated from urethrograms ranged from 12 to 45 mm (mean = 26 mm). RESULTS: Urethroplasties in all patients with bulbar straddle injuries were salvaged by stricture excision and primary anastomosis with corporal separation, and urethroplasties in both patients with pelvic fracture urethral injuries were salvaged by abdominal transpubic perineal urethroplasty. Although the patients who underwent transpubic urethroplasty had transient pelvic girdle pain, no severe complications were observed. All patients were for 10 to 25 months postoperatively (mean = 16 months) able to void satisfactorily without additional treatment. CONCLUSIONS: Failed urethroplasties for traumatic urethral injuries can be salvaged with a second reconstruction surgery. The procedure of choice for this salvage is anastomotic urethroplasty with techniques for tension-free anastomosis.

[The efficacy of direct vision internal urethrotomy for male urethral stricture].

OBJECTIVE: Direct vision internal urethrotomy (DVIU) has been considered to be a low invasive and widely used therapeutic modality for male urethral stricture. However, its efficacy is still controversial. We herein evaluated the efficacy of DVIU for male urethral stricture. PATIENTS AND METHODS: Nineteen patients 27 to 78 years old (median age = 59) underwent DVIU for urethral strictures at our hospital were included in this study. Strictures were at bulbar urethra in 17 patients, membranous urethra in 1 patient, and pendulous urethra in 1 patient. The stricture lengths estimated on retrograde urethrography were less than 1 cm in 13 patients, 1-2 cm in 2 patients, and more than 2 cm in 4 patients. The etiology of stricture was straddle injury in 7 patients, post transurethral surgery in 7 patients, pelvic fracture in 1 patient, and unknown in 4 patients. The operation was done by cold knife incision using guidewire. The duration of postoperative urethral catheterization was 5 to 35 days (mean 12.8 days). Follow up duration ranged from 1 month to 139 months (mean 48.2 months). The definition of postoperative re-stricture was the confirmation of re-stricture on retrograde urethrography or deterioration of symptom. RESULTS: While no severe complication was observed, postoperative re-stricture was seen in 13 patients. Stricture-free rates at 3 months, 6 months, and 5 years after the first DVIU were 44.4%, 38.1%, 20.3% respectively. Although second DVIU was done for 7 patients with re-stricture, six patients resulted in failure. Stricture-free rates at 3 months, 6 months, and 5 years after the second DVIU were 42.2%, 28.6%, 14.3% respectively. Though the third DVIU was done for two of them, they were unable to void just immediately after the removal of urethral catheters. Stricture-free rate in stricture less than 1 cm was higher than that in 1 cm or longer, though it did not reach significant difference (p = 0.1813). CONCLUSION: The efficacy of DVIU is lesser than we expected. DVIU seems to be excessively applied to male urethral strictures and should not be performed for long and recurrent urethral stricture.

A case report of retroaortic left renal vein with tumor thrombus of renal cell carcinoma.

A 75-year-old woman was referred to our department for evaluation of a left renal tumor. Computed tomography and other imaging studies demonstrated a left renal mass and tumor extension into the left renal vein passing caudally behind the aorta. We clinically diagnosed the tumor as renal cell carcinoma (RCC) associated with a retroaortic left renal vein thrombus, and performed a radical nephrectomy. Pathological examination of the surgical specimen showed a grade 2, clear cell carcinoma with a renal vein thrombus and negative surgical margin. Retroaortic left renal vein is a rare anomaly with a prevalence of 1.8-2.4%. RCC associated with a retroaortic left renal vein thrombus is rarer still. To our knowledge, this is only the third case report to describe an RCC associated with a tumor thrombus in the retroaortic left renal vein.

Glucose-regulated protein 78 positivity as a predictor of poor survival in patients with renal cell carcinoma.

INTRODUCTION: Glucose-regulated protein 78 (GRP78), a chaperone for newly formed proteins during folding and glycosylation, is associated with resistance to apoptosis in some forms of cancer. We assessed GRP78 expression and its correlation with clinicopathological parameters and survival. PATIENTS AND METHODS: Immunohistochemistry was performed using formalin-fixed, paraffin-embedded specimens: 128 primary renal cell carcinoma (RCC) specimens (120 conventional and 8 other cell types) and 9 metastatic specimens. GRP78 positivity was determined based on intensity of staining and percentage of cells stained. Correlation of GRP78 positivity with clinicopathological parameters including patients' survival was evaluated. RESULTS: A statistically significant association was found between GRP78 positivity and higher tumor grade (G3; p <0.0001), advanced T stage (≥pT3; p = 0.0002), lymphovascular invasion (positive; p <0.0001), regional nodal involvement (≥N1; p = 0.0086), and distant metastases at presentation (M1; p = 0.001). Positivity of GRP78 expression was significantly associated with shorter disease-specific survival and shorter progression-free survival. Cox proportional hazard model showed that strong GRP78 positivity was an independent predictor of shortened progression-free survival in N0M0 RCC patients. CONCLUSIONS: There was a significant relationship between GRP78 expression levels and aggressiveness of RCC. Increased expression of GRP78 might be a useful parameter to predict shortened survival in patients with RCC.

[Clinical experience of 52 patients undergoing laparoscopic radical prostatectomy].

Perioperative results and oncological and functional results were evaluated for 52 patients who underwent laparoscopic radical prostatectomy (LRP). Median operative time was 341 minutes and median blood loss was 828 ml. The intraoperative complications were hemorrhage exceeding 3,000 ml (five cases), ureteral injury (two cases), and rectal injury (one case). The median day of catheter removal was postoperative day 7. Postoperative complications were temporal arrhythmia, mild hydronephrosis, port site hernia, urethral stricture, and a giant lymphocele. When surgical results were compared between the firsthalf cases and second-half cases who were operated on by a single surgeon, median operative time and intraoperative hemorrhage did not differ significantly between the two halves but the day of catheter removal after LRP was significantly earlier for the second-half group. The pathological stage was pT3 in 41.2% of the patients and the negative surgical margin rate was 62.7%. The 3-year PSA-failure-free survival rate was 64. 1%. Pad-free status (0-1 pad/day) was achieved in 84.4% of the patients. Erectile function was preserved in 58.3% of patients undergoing nerve-sparing LRP. Although the complication rate and the quality of operative procedures gradually improved, efforts to improve the oncological and functional outcomes of LRP must continue.

Adrenomedullin increases renal nitric oxide production and ameliorates renal injury in mice with unilateral ureteral obstruction.

PURPOSE: We evaluated the effects of adrenomedullin (Peptide Institute, Minoh-shi, Osaka, Japan) on mediators, including nitric oxide and transforming growth factor-beta, and parameters of renal injury in a murine unilateral ureteral obstruction model. MATERIALS AND METHODS: Three study groups of control, adrenomedullin treated and adrenomedullin plus L-NAME treated BALB/C mice, respectively, underwent left unilateral ureteral obstruction. A 24-hour urine sample was collected to measure urinary NO(2)/NO(3) 1 day before unilateral ureteral obstruction and kidneys were harvested on postoperative day 14. Tubulointerstitial damage markers were evaluated by immunohistochemistry. Tissue transforming growth factor-beta was determined by enzyme-linked immunosorbent assay. Endothelial and inducible nitric oxide synthase immunolocalization was also determined. RESULTS: Urinary NO(2)/NO(3) was significantly higher in the adrenomedullin group than in controls, confirming increased renal nitric oxide production. Immunohistochemistry showed increased endothelial nitric oxide synthase in vascular endothelial cells in the adrenomedullin group but tissue transforming growth factor-beta did not significantly differ in controls vs the adrenomedullin group. Interstitial collagen deposition and fibroblasts in the obstructed kidney were significantly decreased in the adrenomedullin group. The number of leukocytes and apoptotic cells in the obstructed kidney were significantly decreased by adrenomedullin. Renal injury amelioration resulting from adrenomedullin was blunted by the nitric oxide synthase inhibitor L-NAME. CONCLUSIONS: Adrenomedullin increased renal nitric oxide, and suppressed tubular apoptosis, interstitial fibrosis and inflammatory cell infiltration in mice with unilateral ureteral obstruction. The renoprotective peptide adrenomedullin may be useful for that condition.

Severe polyuria after the resection of adrenal pheochromocytoma.

A 73-year-old male patient with hypertension and hyperglycemia was referred to our hospital because of a diagnosis regarding his left adrenal tumor. Because the levels of urinary metanephrine and normetanephrine were elevated, and (131) I-MIBG scintigraphy showed intense uptake in the adrenal tumor, the tumor was diagnosed as a pheochromocytoma. An adrenalectomy was carried out. Severe polyuria, which was accompanied by a rapid decrease in central venous pressure, started 1 hour after the operation. Urine output of more than 8000 mL/day continued until the 16th postoperative day. Plasma antidiuretic hormone (ADH) levels were within the normal range. Plasma human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) were elevated postoperatively, and the elevation of these peptides was one possible cause for the severe polyuria. Because ADH levels in the tumor fluid were not elevated, the tumor was not an ADH-secreting tumor. Urinary ß2-microglobulin was significantly elevated after the operation, thus suggesting that renal tubule dysfunction might also have been involved in the polyuria. However, the mechanism of polyuria after the resection of adrenal pheochromocytoma is not fully understood. Polyuria after the resection of adrenal pheochromocytoma is extremely rare, and the present subject is the second case to date.

[Spontaneous rupture of the ureter as the primary symptom of malignant lymphoma].

We report a rare case in which upper ureteral rupture was the primary symptom of malignant lymphoma. A 74-year-old female visited our hospital with left flank pain. Computed tomography showed urinoma around the left kidney and retrograde pyelography showed a diffuse filling defect in the left ureter and a rupture of the upper portion of that ureter. A urine cytology specimen from the left ureter was class V, suggesting undifferentiated carcinoma or malignant lymphoma. An open laparotomy revealed a nodule on the omentum and diffuse fibrosis around both ureters, and the histopathological diagnosis was diffuse large B-cell lymphoma. The patient' s ureteral stenosis disappeared after she received six cycles of R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone and rituximab) chemotherapy. We should be aware that malignant lymphoma can be the cause of a spontaneous ureteral rupture.

[Clinical experience of treatment of liver metastasis of renal cell carcinoma treated with SMANCS/Lipiodol therapy].

The treatment for metastatic renal cell carcinoma (RCC) has changed dramatically after the beginning of molecular-targeted therapies. However,the treatment for liver metastasis is still difficult in patients with metastatic RCC. We treated liver metastases (8 target lesions) of RCC with stylene-maleic acid neocarzinostatin (SMANCS)/Lipiodol therapy. At the treatment procedure,a catheter was inserted at the femoral artery (Seldinger's method),a microcatheter was selectively inserted into the branch of hepatic artery which fed the liver metastasis,and then SMANCS/Lipodol was infused. We treated 1,2 and 1 patient 4,2, and 1 time,respectively. One lesion treated with SMANCS/Lipodol was further treated by radiofrequency ablation 13 days later. Of 6 metastatic lesions which could be followed up for more than 6 months after the treatment,one had partial response for 4 months and 4 had stable disease for more than 6 months. Four of the 6 lesions shrunk after SMANCS/Lipiodol treatment. Two of 4 patients survived more than 18 months after the first SMANCS/Lipiodol therapy. In all 9 SMANCS/Lipiodol treatments,grade 1 liver dysfunction (44.4%),ascites (11.1%) and fatigue (11.1%) occurred after the treatments. These adverse events were all improved by conservative treatments. SMANCS/Lipiodol therapy can be a treatment option as local treatment for liver metastasis of RCC.

[Case of primary amelanotic malignant melanoma of the female urethra].

We report a rare case of primary amelanotic malignant melanoma of the female urethra. A 58-year-old female with complaint of nodule on the external urethral meatus was referred to our hospital. Pathological diagnosis of the biopsy specimen from the nodule was malignant melanoma. Computed tomography of the chest and abdomen as well as bone scan showed no evidence of metastasis. Sentinel biopsy from the inguinal lymph nodes revealed no metastasis. Thereafter, the patient underwent radical urethrectomy, whose limits of resection were the bulbocavernosal muscles bilaterally, the arch of the pubic symphysis anteriorly, the anterior vaginal wall posteriorly, and the urethra up to the level of the bladder neck superiorly. The histopathological diagnosis was amelanotic malignant melanoma of the urethra. The patient had received six cycles of DAV-Feron (dacarbazine, nimustine, vincristine, and interferon-beta) in an adjuvant setting, and there is no sign of recurrence 25 months after operation.

[Oral mucosa graft urethroplasty for complicated urethral strictures].

OBJECTIVE: We evaluated the efficacy and outcome of one-stage oral mucosa graft urethroplasty, which is currently the procedure of choice for treating lengthy and complicated urethral strictures not amenable to excision and primary end-to-end anastomosis. PATIENTS AND METHODS: Seven patients 33 to 74 years old (mean age = 53.7) underwent one-stage oral mucosa graft urethroplasty for a stricture in either the bulbar urethra (four patients), penile urethra (two patients), or pan-anterior urethra (one patient). Three of the strictures were due to trauma, one was due to inflammation, and one was due to a failed hypospadia repair. The other two were iatrogenic. All patients had previously undergone either internal urethrotomy or repeated urethral dilation. Three patients received a tube graft, three received a ventral onlay, and one received a dorsal onlay. A free graft of oral mucosa was harvested from the inside of each patient's left cheek, and if necessary to obtain a sufficient length, the harvest was extended to include mucosa from the lower lip and the right cheek. The graft lengths ranged from 2.5 to 12 cm (mean = 4.6 cm). A urethral catheter was left in place for 3 weeks postoperatively. RESULTS: While no severe complications at the donor site were observed during follow-up periods ranging from 3 to 55 months (mean = 14 months), two patients who had received a tube graft developed distal anastomotic ring strictures that were managed by internal urethrotomy. The other five required no postoperative urological procedure even though one who had received a ventral onlay developed a penoscrotal fistula. CONCLUSION: Oral mucosa is an ideal urethral graft, and oral mucosa graft urethroplasty is an effective procedure for repairing complicated urethral strictures involving long portions of the urethra.

Clinical impact of the presence of the worst nucleolar grade in renal cell carcinoma specimens.

OBJECTIVE: Renal cell carcinoma (RCC) with a high-nucleolar-grade component is considered to be an aggressive type of tumor. In the present study, we evaluated the impact of the presence of the worst-nucleolar-grade component and also tried to determine predictors for recurrence and prognosis in patients with the worst grade component. METHODS: We evaluated 314 patients with RCC. A three-graded system was used for nucleolar grading, the patients were classified into four groups according to the presence of the worst nucleolar grade (Grade 3) and the occupancy of each grade, and clinicopathological factors and clinical outcomes were compared. In patients of Grade 3 components (Groups 1 and 2), factors influencing on prognosis and recurrence were evaluated by multivariate analysis. RESULTS: There was no significant difference in clinicopathological factors between Group 1 (with Grade 3-dominant tumors) and Group 2 (with tumors in which Grade 1 or 2 was dominant and there were Grade 3 components). Neither did cause-specific survival or recurrence-free survival differ significantly between those two groups. In multivariate analysis, only distant metastasis was an independent predictor for prognosis in all patients with Grade 3 components. Moreover, an elevated C-reactive protein (CRP) level (>or=1 mg/dl) was the only independent predictor of recurrence in N0M0 patients. CONCLUSIONS: Regardless of dominancy, the presence of the worst grade component has a significant clinical impact in RCC patients. N0M0 patients whose RCC has worst-grade components but whose CRP levels are <1 are expected to have longer recurrence-free intervals and to survive longer than those whose CRP levels are higher.

Bilateral adrenal leiomyosarcoma treated with multiple local therapies.

A 62-year-old woman presented with right flank pain, and computed tomography (CT) showed bilateral adrenal tumors (right, 8 cm; left, 4 cm). There were no abnormal findings on physical examination, and adrenal hormone levels in serum and urine were within normal limits. Radiological studies showed a right adrenal tumor with intratumoral hemorrhage, a cystic tumor in the left adrenal gland, and no sign of distant metastasis. Because laboratory tests showed normal levels of adrenal hormones, we considered the tumors to be nonfunctioning adrenal tumors. The right adrenal tumor was surgically removed because it was thought to be malignant, and histological examination revealed that it was a leiomyosarcoma. Postoperative CT showed a pleural metastasis in the right chest wall. The patient received combination chemotherapy with cyclophosphamide, vincristine, adriamycin, and dacarbazine. The metastasis was also treated with radiofrequency ablation (RFA). Because the left adrenal tumor grew rapidly despite two courses of the chemotherapy, it too was surgically removed. After the operation, metastasis in the right iliac bone was treated with RFA and radiotherapy. Positron emission tomography detected bilateral femoral metastases, and these were treated with radiotherapy in combination with a low dose of cisplatin. A liver metastasis and a small metastasis in the left kidney were treated with RFA and a metastasis in the pancreatic tail was removed surgically. Sixteen months after the right adrenalectomy, the patient died due to systemic spread of the disease. Multiple local treatments including RFA, radiotherapy, and resection were effective for the local control of metastatic lesions of adrenal leiomyosarcoma.

[Severe hypoglycemia after resection of adrenal pheochromocytoma: a case report].

A 55-year-old female presented with subarachnoid hemorrhage and was admitted to the department of neurosurgery. Because she had severe hypertension, systemic evaluation was performed. Computed tomography showed a right adrenal tumor which was suspected to be a pheochromocytoma because catecholamine levels were very high in both serum and 24-hour urine. She did not awaken from anesthesia after laparoscopic adrenalectomy and laboratory tests showed that her blood sugar concentration was 33 mg/dl. This hypoglycemia was controlled by continuous infusion of a 50% glucose solution at 40 ml/h and she became conscious the next morning. We gradually decreased the amount of glucose infused and stopped the infusion on postoperative day 4. The tumor was pathologically diagnosed as a pheochromocytoma.

[Two cases of unilateral adrenalectomy for bilateral adrenal Cushing syndrome].

For treatment of bilateral adrenal Cushing syndrome (CS) unilateral adrenalectomy (UAdx) is less invasive than bilateral adrenalectomy and lifetime replacement of glucocorticoids can be avoided. Laparoscopic UAdxs was performed on 2 patients with bilateral adrenal CS. In both cases, symptoms associated with CS were improved after UAdx. Although serum adrenocorticotropic hormone levels remained lower than normal after UAdxs, cortisol levels in both serum and urine have been maintained within normal ranges for more than 1 year in both cases.

[Case of pelvic retroperitoneal fibrosis].

A 66-year-old man visited his nearby clinic with a complaint of left lower abdominal pain. Abdominal CT scan showed left hydronephrosis due to lower ureteral involvement by infiltrative retroperitoneal mass located outside of the left posterior wall of the bladder and left seminal vesicle. He was referred to our hospital for further examination. Pathological diagnosis of the percutaneous CT-guided biopsy of retroperitoneal mass was fibrosis without any malignant tumor. Because we could not rule out the possibility of the secondary fibrosis accompanied by malignant tumor, we performed surgical resection of the retroperitoneal mass involving left ureter and confirmed that the mass contains no malignant tumor by frozen section analysis. We augmented the defected ureter by Boari flap method. We should be noticed that retroperitoneal fibrosis could be a differential diagnosis of retroperitoneal pelvic mass.

Fatty acid synthase over expression is an indicator of tumor aggressiveness and poor prognosis in renal cell carcinoma.

PURPOSE: Fatty acid synthase is a key enzyme in the de novo biosynthesis of fatty acids. Increased fatty acid synthase expression and its association with tumor aggressiveness and poor prognosis have been demonstrated in various human malignant tumors. We investigated fatty acid synthase expression in patients with renal cell carcinoma and its impact on clinicopathological parameters. MATERIALS AND METHODS: Fatty acid synthase expression in 120 patients with renal cancer was examined by immunohistochemistry. The relationship between fatty acid synthase expression status and various clinicopathological parameters was analyzed. Survival analysis was performed using the log rank test and a Cox multivariate hazard model. RESULTS: Of 120 tumors 18 (15%) showed positive fatty acid synthase expression, which was significantly associated with advanced pathological T stage (pT3-4, p = 0.0009), regional lymph node metastasis (p = 0.0429), distant metastasis (p = 0.0042), higher histological grade (G3, p = 0.0017) and microvascular invasion (p = 0.0357). Patients with positive fatty acid synthase expression had significantly shorter cancer specific survival than those with negative FAS expression (p <0.0001). Multivariate Cox proportional hazards model analysis demonstrated that positive fatty acid synthase expression was an independent predictor of shortened cancer specific survival (p = 0.0363, HR 3.736). CONCLUSIONS: Increased FAS expression could be an indicator of tumor aggressiveness and poor prognosis of renal cell carcinoma. Patients with fatty acid synthase positive tumors should be followed closely and carefully, and adjuvant therapy should be considered.

Pharmacological inhibitor of fatty acid synthase suppresses growth and invasiveness of renal cancer cells.

PURPOSE: Fatty acid synthase has been shown to be over expressed in a wide range of cancers and it has emerged as a therapeutic target. We examined whether fatty acid synthase could be a novel therapeutic target for renal cell carcinoma using the pharmacological fatty acid synthase inhibitor C75 (Cayman Chemical, Ann Arbor, Michigan). MATERIALS AND METHODS: The effects of C75 on cell viability and proliferation in human renal cancer 769P (ATCC(R)), Caki-1 and KU20-01 cells were examined by MTS assay and cell counts. Cell cycle distribution was analyzed by flow cytometry and cell invasiveness was assessed by wound healing and Matrigel(trade mark) invasion assays. Fatty acid synthase expression and the effects of C75 on intracellular signaling pathways were analyzed by Western blotting. The antitumor efficacy of C75 was examined using Caki-1 cell xenografts. RESULTS: All renal cancer cell lines expressed detectable fatty acid synthase. C75 (10 mug/ml) significantly inhibited cell viability and growth by arresting the cell cycle at the G2/M phase and inducing apoptosis (p <0.01). The covered area in the wound and the number of cells invading through a Matrigel chamber were significantly smaller for cells treated with C75 than they were for control cells treated with vehicle (p <0.001). C75 suppressed Her2 and epidermal growth factor receptor expression as well as STAT3 phosphorylation, while increasing p53 and p21(Waf1/Cip1) expression. Intraperitoneal administration of C75 at doses of 20 mg/kg per week for 28 days significantly reduced the tumor volume of Caki-1 xenografts (p <0.05). CONCLUSIONS: Pharmacological inhibition of fatty acid synthase could be an effective strategy for treating renal cell carcinoma.

Topotecan and small interfering RNA suppress survivin expression synergistically in Caki-1 renal cancer cells: Direct suppression of survivin and enhancement of transfection efficiency by topotecan.

Survivin is an apoptosis inhibitor found in many tumors but not in most normal differentiated tissues, which makes it an exciting target for cancer therapy. Survivin expression has been shown to be associated with cell proliferation in renal cancer and we previously demonstrated the possibility of treating renal cancer with survivin-specific siRNA and topotecan, which increased the uptake of siRNA by KU19-20 renal cancer cells. We found in the present study that the combination of siRNA and topotecan inhibits survivin expression in Caki-1 renal cancer cells by another mechanism. Caki-1 renal cancer cells expressed higher level of survivin than KU19-20 cells did and survivin-specific siRNA alone suppressed survivin expression only slightly. The combination of topotecan and siRNA suppressed survivin expression completely and inhibited cell proliferation. Topotecan itself did not increase cellular uptake of siRNA but suppressed survivin expression. It also increased transfection efficiency without increasing cellular uptake of siRNA. Although the mechanism of action varies between cell lines, combination therapy using topotecan and siRNA should offer an attractive approach for treatment of advanced renal cancer.