[Show abstract][Hide abstract] ABSTRACT: The purpose of this work was to report measured catheter displacement prior to the delivery of high-dose-rate brachytherapy (HDR) in the treatment of prostate cancer.
Journal of Contemporary Brachytherapy 06/2014; 6(2):161-6.
[Show abstract][Hide abstract] ABSTRACT: GLIPR1 is a p53 target gene known to be downregulated in prostate cancer, and increased endogenous GLIPR1 expression has been associated with increased production of reactive oxygen species, increased apoptosis, decreased c-Myc protein levels and increased cell cycle arrest. Recently, we found that upregulation of GLIPR1 in prostate cancer cells increases mitotic catastrophe through interaction with heat shock cognate protein 70 (Hsc70) and downregulation of Aurora kinase A and TPX2. In this study, we evaluated the mechanisms of recombinant GLIPR1 protein (glioma pathogenesis-related protein 1-transmembrane domain deleted [GLIPR1-ΔTM]) uptake by prostate cancer cells and the efficacy of systemic GLIPR1-ΔTM administration in a prostate cancer xenograft mouse model. GLIPR1-ΔTM was selectively internalized by prostate cancer cells, leading to increased apoptosis through reactive oxygen species production and to decreased c-Myc protein levels. Interestingly, GLIPR1-ΔTM was internalized through clathrin-mediated endocytosis in association with Hsc70. Systemic administration of GLIPR1-ΔTM significantly inhibited VCaP xenograft growth. GLIPR1-ΔTM showed no evidence of toxicity following elimination from mouse models 8 hr after injection. Our results demonstrate that GLIPR1-ΔTM is selectively endocytosed by prostate cancer cells, leading to increased reactive oxygen species production and apoptosis, and that systemic GLIPR1-ΔTM significantly inhibits growth of VCaP xenografts without substantial toxicity.
International Journal of Cancer 04/2014; 134(8):2003-13. · 6.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Treating adrenal metastases from primary malignancies with laparoscopic adrenalectomy (LA) remains controversial. The aim of this study was to evaluate the feasibility, effectiveness and efficiency of LA for solitary adrenal metastasis.
From November 2003 to September 2012, eight consecutive patients with adrenal metastasis were treated with LA. A retrospective study was conducted, and clinical and histological data were analyzed.
All LA were successfully performed. There were no major complications, blood transfusions or conversions to open adrenalectomy. The patients included seven men and one woman with a median age of 59 years at the time of operation. Adrenal metastases were most commonly noted to be from non-small-cell lung cancer (four patients) and renal cell carcinoma (four patients). The majority of adrenal metastases were unilateral (right: one patient; left: seven patients). One patient had bilateral metastases. The median overall survival was 14 months. Four patients (two with non-small-cell lung cancer; two with renal cell carcinoma) were alive with no evidence of metastatic disease as of October 2013.
LA is a safe and effective procedure for patients with isolated metastases. Surgical resection with LA for a solitary adrenal metastasis from primary malignancy can achieve a good prognosis.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent (192)Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow-up was 61 months (range, 25-94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach.
Journal of Radiation Research 11/2013; · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: The objective of this study is to clarify whether symphysiotomy is an essential procedure combined with the laparoscopic pyeloplasty for the surgical treatment of ureteropelvic junction obstruction related to horseshoe kidney. METHODS: We retrospectively reviewed five horseshoe kidney patients with symptomatic hydronephrosis who underwent laparoscopic transperitoneal Anderson-Hynes pyeloplasty without symphysiotomy between July 2002 and October 2011. RESULTS: All procedures were completed successfully without open conversion. Mean operative time and estimated blood loss were 209 min and 40 mL, respectively. Anterior crossing vessels were observed in all cases, and four of them were defined as a principle cause of the obstruction. In the remaining case, intrinsic stenosis of the ureteropelvic junction was noted. Crossing vessels were transposed behind the ureter with ureteropelvic anastomosis at the anterior aspect of these structures. Preoperative symptoms were absent postoperatively in all cases. Diuretic renogram showed that renal function of the side with hydronephrosis was unchanged, but diuretic excretion half-time was diminished in all cases. CONCLUSION: The present data suggest that symphysiotomy can be avoided in many, if not all, cases of hydronephrosis related to horseshoe kidney. Laparoscopic Anderson-Hynes pyeloplasty with transposition of anterior crossing vessels seems effective, especially if aberrant vessels are strongly suspected to be present from the preoperative imaging examination.
[Show abstract][Hide abstract] ABSTRACT: Aims: Inflammatory myofibroblastic tumor (IMT) of the urinary bladder is a clinically and histologically uncommon benign tumor that can be easily mistaken for a malignant neoplasm. We sought to determine whether immunohisto-chemical staining would be evaluated IMT of the urinary bladder. We have also shown the literatures that imminohis-tochemical staining of IMT was investigated to distinguish malignant lesions using PubMed data base. Methods: Im-munohistochemical staining, including anaplastic lymphoma kinase (ALK), p53, cytokeratin, vimentin, desmin, al-pha-smooth muscle actin, myoglobin, smooth muscle myosin and S100, was carried out on serial sections from archival specimens of three patients who underwent transurethral resection and partial cystectomy. Results: Immunohistchemi-cal staining in all patients was positive for ALK and weak positive for p53 protein. In the literatures, positive rates of ALK and p53 in the IMT of the urinary bladder were 60.9% and 53.1%, respectively. Sarcoma and carcinosarcoma were shown in the pathological specimens with negative ALK and strongly positive p53 in the same data base. Conclu-sions: Both ALK and p53 were potentially useful protein markers to distinguish between IMT and sarcoma. However, this study was small sample size. Further study was warranted an investigation of the availability of these proteins in IMT.
[Show abstract][Hide abstract] ABSTRACT: We investigated the effect of dasatinib and sunitinib on tyrosine kinase (TK) signaling, caveolin-1 (Cav-1) expression and secretion and proliferation of PC-3 and DU145 prostate cancer cells in vitro and in vivo. Treatment of both cell lines with either dasatinib or sunitinib reduced phosphorylation of PDGFR, VEGFR2, Akt, FAK, Src (dasatinib only) and Cav-1, and reduced cellular and secreted levels of Cav-1. Both agents dose-dependently inhibited proliferation of these cells. In PC-3 and DU145 subcutaneous xenografts, treatment with dasatinib, sunitinib or anti-Cav-1 antibody (Ab) alone produced significant tumor regression compared with that by vehicle or IgG alone. Combined dasatinib and anti-Cav-1 Ab treatment or sunitinib and anti-Cav-1 Ab produced greater tumor regression than either treatment alone. Serum Cav-1 levels were lower in dasatinib- and sunitinib-treated mice than they were in vehicle-treated mice, and correlated positively with tumor growth in dasatinib- and sunitinib-treated groups (r = 0.48, p = 0.031; r = 0.554, p = 0.0065, respectively), compared with vehicle controls. Cav-1 knockdown, in combination with dasatinib or sunitinib treatment in PC-3 cells, caused a greater reduction in the phosphorylation of PDGFR-β and VEGFR2, and expression and secretion of PDGF-B and VEGF-A than that in PC-3 cells treated with dasatinib or sunitinib alone in control siRNA cells, suggesting that Cav-1 is involved in an autocrine pathway that is affected by these drugs. Overall, our results suggest a role for Cav-1 as a biomarker of response to both dasatinib and sunitinib treatment and as a therapeutic target in prostate cancer.
Cancer biology & therapy 10/2012; 14(2). · 3.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Approximately 80% of patients with prostate cancer will develop bone metastases, which often lead to bone pain and skeletal-related events. Sr-89 is an established alternative for the palliation of bone pain in prostate cancer. We aimed to assess the effect of Sr-89 radionuclide therapy on quality of life (QOL) in prostate cancer patients with painful bone metastases.
Thirteen patients received a single intravenous injection of Sr-89 at a dose of 2.0 MBq/kg. All patients underwent QOL evaluation prior to Sr-89 treatment and 1, 2, and 3 months afterward using the Japanese version of the EORTC QLQ-BM22, EORTC QLQ-C30, a VAS, and face scale. We also evaluated PSA and ALP response and toxicity of the Sr-89 therapy.
The pain characteristics subscale of the EORTC QLQ-BM22 was significantly reduced from 1 month onward compared with the baseline. The functional interference and psychosocial aspects subscales were significantly higher than baseline from 2 months onward. At 2 months, VAS indicated a significant reduction in pain as compared to the baseline. Sr-89 therapy caused a nonsignificant reduction in PSA and ALP levels. No patients had leukocyte toxicity, and one patient had grade 3 platelet toxicity.
Sr-89 radionuclide therapy can provide not only reduced pain characteristics but also better psychosocial aspects and functional interference in patients with painful bone metastases of prostate cancer.
Annals of Nuclear Medicine 04/2012; 26(6):485-91. · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previously we reported caveolin-1 (Cav-1) overexpression in prostate cancer cells and showed that it promotes prostate cancer progression. Here, we report that Cav-1 was overexpressed in 41.7% (15 of 36) of human high-grade prostatic intraepithelial neoplasia (HGPIN) specimens obtained during radical prostatectomies. Positive correlations exist between Cav-1-positive (Cav-1(+)) HGPIN and Cav-1(+) primary prostate cancer (rho = 0.655, P < 0.0001) and between Cav-1 and c-Myc expression in HGPIN (rho = 0.41, P = 0.032). To determine whether Cav-1 cooperates with c-Myc in development of premalignant lesions and prostate cancer in vivo, we generated transgenic mice with c-Myc overexpression driven by the ARR(2)PB promoter. In this ARR(2)PB-c-myc model, Cav-1 overexpression was found in mouse PIN (mPIN) lesions and prostate cancer cells and was associated with a significantly higher ratio of proliferative to apoptotic labeling in mPIN lesions than in the Cav-1-negative epithelia adjacent to those lesions (10.02 vs. 4.34; P = 0.007). Cav-1 overexpression was also associated with increased levels of P-Akt and VEGF-A, which were previously associated with Cav-1-induced prostate cancer cell survival and positive feedback regulation of cellular Cav-1 levels, respectively. In multiple prostate cancer cell lines, Cav-1 protein (but not mRNA) was induced by c-Myc transfection, whereas VEGF siRNA transfection abrogated c-Myc-induced Cav-1 overexpression, suggesting a c-Myc-VEGF-Cav-1 signaling axis. Overall, our results suggest that Cav-1 is associated with c-Myc in the development of HGPIN and prostate cancer. Furthermore, Cav-1 overexpression in HGPIN is potentially a biomarker for early identification of patients who tend to develop Cav-1(+) primary prostate cancer.
Molecular Cancer Research 12/2011; 10(2):218-29. · 4.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Multiple studies have demonstrated overexpression of caveolin-1 (Cav-1) in prostate cancer (PCa) cells and its association
with disease progression. In PCa cells, Cav-1 serves multiple diverse functions that appear to be unique in tumor biology.
Within those, elevated Cav-1 may lead to the formation of aberrant signaling scaffolds and may actively participate as a signaling
molecule. In addition, overexpression of Cav-1 can induce mRNA levels for specific growth factors (GFs), including vascular
endothelial GF, transforming GF-β1, and fibroblast GF2, through Akt activities. Importantly, these specific GFs can, in turn,
stimulate expression of Cav-1. It is notable that Cav-1 is secreted by PCa cells and that secreted Cav-1 can be taken up by
adjacent PCa cells and tumor-associated endothelial cells, through which the tumor-promoting activities of Cav-1 “spread”
throughout the tumor microenvironment. Because secreted Cav-1 can enter the blood, the tumor-promoting effects of Cav-1 also
manifest at distant sites of metastasis. The pervasive effects of Cav-1 lead to the establishment of a positive-feedback loop
that promotes PCa progression through unprecedented effects on the local and metastatic tumor microenvironments. This chapter
is a brief discussion of the complex, context-dependent activities of Cav-1, and delineation of its oncogenic functions within
the context of PCa.
[Show abstract][Hide abstract] ABSTRACT: GLIPR1 is upregulated by p53 in prostate cancer cells and has preclinical antitumor activity. A phase I clinical trial was conducted to evaluate the safety and activity of the neoadjuvant intraprostatic injection of GLIPR1 expressing adenovirus for intermediate or high-risk localized prostate cancer before radical prostatectomy (RP).
Eligible men had localized prostate cancer (T1-T2c) with Gleason score greater than or equal to 7 or prostate-specific antigen 10 ng/mL or more and were candidates for RP. Patients received the adenoviral vector expressing the GLIPR1 gene by a single injection into the prostate followed four weeks later by RP. Six viral particle (vp) dose levels were evaluated: 10(10), 5 × 10(10), 10(11), 5 × 10(11), 10(12), and 5 × 10(12) vp.
Nineteen patients with a median age of 64 years were recruited. Nine men had T1c, 4 had T2a, and 3 had T2b and T2c clinical stage. Toxicities included urinary tract infection (n = 3), flu-like syndrome (n = 3), fever (n = 1), dysuria (n = 1), and photophobia (n = 1). Laboratory toxicities were grade 1 elevated AST/ALT (n = 1) and elevations of PTT (n = 3, with 1 proven to be lupus anticoagulant). No pathologic complete remission was seen. Morphologic cytotoxic activity, induction of apoptosis, and nuclear p27(Kip1) upregulation were observed. Peripheral blood CD8(+), CD4(+), and CD3(+) T-lymphocytes were increased, with upregulation of their HLA-DR expression and elevations of serum IL-12.
The intraprostatic administration of GLIPR1 tumor suppressor gene expressed by an adenoviral vector was safe in men, with localized intermediate or high-risk prostate cancer preceding RP. Preliminary evidence of biologic antitumor activity and systemic immune response was documented.
Clinical Cancer Research 09/2011; 17(22):7174-82. · 7.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the prevalence of fluoroquinolone-resistant Escherichia coli before transrectal ultrasound (TRUS)-guided prostate biopsy and prospectively analyze the rates of infective complications after biopsy in patients receiving fluoroquinolone prophylaxis. E. coli is the pathogen most commonly associated with infections after TRUS-guided prostate biopsy, and the prevalence of fluoroquinolone-resistant E. coli is increasing.
We analyzed the prospective data from 100 patients who underwent TRUS-guided prostate biopsy from April to December 2010. A stool culture was obtained 1 month before biopsy. Patients received 500 mg levofloxacin orally once daily for 3 days, beginning 2 hours before biopsy. All biopsies were performed as outpatient procedures.
Of the 100 patients, 13 (13%) had a stool culture positive for fluoroquinolone-resistant E. coli. In 4 (31%) of these 13 patients, acute bacterial prostatitis was detected after TRUS-guided prostate biopsy. Of the 87 patients whose stool culture was negative for fluoroquinolone-resistant E. coli, none had acute bacterial prostatitis. All 13 infected patients were treated with carbapenems immediately after diagnosis of prostatitis and made a complete recovery.
Prophylactic fluoroquinolone is still effective in preventing acute bacterial prostatitis after TRUS-guided prostate biopsy. The incidence is relatively low in patients with fluoroquinolone-sensitive E. coli. However, the prevalence of fluoroquinolone-resistant E. coli is about 13% in this population. Stool cultures for the detection of fluoroquinolone-resistant E. coli might be obtained before TRUS-guided prostate biopsy.
[Show abstract][Hide abstract] ABSTRACT: We analyzed the effects of castration on epididymal white adipose tissue (WAT) in C57BL/6J mice which were fed a regular or high-fat diet. Fourteen days following surgical castration profound effects on WAT tissue such as reductions in WAT wet weight and WAT/body weight ratio, induction of lipolysis and morphologic changes characterized by smaller adipocytes, and increased stromal cell compartment were documented in both dietary groups. Castrated animals had decreased serum leptin levels independent of diet but diet-dependent decreases in serum adiponectin and resistin. The castrated high-fat group had dramatically lower serum triglyceride levels. Immunohistochemical analysis revealed higher staining for smooth muscle actin, macrophage marker Mac-3, and Cxcl5 in the castrated than in the control mice in both dietary groups. We also detected increased fatty-acid synthase expression in the stromal compartment of WAT in the regular-diet group. Castration also reduces the expression of androgen receptor in WAT in the regular-diet group. We conclude that castration reduces tissue mass and affects biologic function of WAT in mice.
Molecular and Cellular Endocrinology 07/2011; 345(1-2):58-67. · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We previously identified the mouse and human Glipr1 and GLIPR1/RTVP-1 genes, respectively, as direct p53 targets with proapoptotic activities in various cancer cell lines, including prostate cancer (PCa). Intratumoral injection of an adenoviral vector capable of efficient transduction and expression of Glipr1 (AdGlipr1) yielded promising therapeutic results in an orthotopic, metastatic mouse model of PCa. AdGlipr1-transduced macrophages (Mφ/Glipr1) generated greater surface expression of CD40, CD80 and major histocompatibility complex class II molecules and greater production of interleukin 12 (IL-12) and IL-6 in vitro than control macrophages did. Mechanistic analysis indicated that increased production of IL-12 in Mφ/Glipr1 depends on activation of the p38 signaling cascade. Mφ/Glipr1 injected into orthotopic 178-2BMA tumors in vivo resulted in significantly suppressed prostate tumor growth and spontaneous lung metastases and longer survival relative to those observed in control-treated mice. Furthermore, these preclinical data indicate the generation of systemic natural killer cell activity and tumor-specific cytotoxic T lymphocyte responses. Trafficking studies confirmed that intratumorally injected Mφ/Glipr1 could migrate to draining lymph nodes. Overall, our data suggest that this novel gene-modified cell approach is an effective treatment avenue that induces antitumor immune responses in preclinical studies.
[Show abstract][Hide abstract] ABSTRACT: Previously, we reported that caveolin-1 (cav-1) is overexpressed in metastatic prostate cancer and that virulent prostate cancer cells secrete biologically active cav-1. We also showed that cav-1 expression leads to prosurvival activities through maintenance of activated Akt and that cav-1 is taken up by other cav-1-negative tumor cells and/or endothelial cells, leading to stimulation of angiogenic activities through PI-3-K-Akt-eNOS signaling. To analyze the functional consequences of cav-1 overexpression on the development and progression of prostate cancer in vivo, we generated PBcav-1 transgenic mice. Adult male PBcav-1 mice showed significantly increased prostatic wet weight and higher incidence of epithelial hyperplasia compared with nontransgenic littermates. Increased immunostaining for cav-1, proliferative cell nuclear antigen, P-Akt, and reduced nuclear p27(Kip1) staining occurred in PBcav-1 hyperplastic prostatic lesions. PBcav-1 mice showed increased resistance to castration-induced prostatic regression and elevated serum cav-1 levels compared with nontransgenic littermates. Intraprostatic injection of androgen-sensitive, cav-1-secreting RM-9 mouse prostate cancer cells resulted in tumors that were larger in PBcav-1 mice than in nontransgenic littermates (P = 0.04). Tail vein inoculation of RM-9 cells produced significantly more experimental lung metastases in PBcav-1 males than in nontransgenic male littermates (P = 0.001), and in cav-1(+/+) mice than in cav-1(-/-) mice (P = 0.041). Combination treatment with surgical castration and systemic cav-1 antibody dramatically reduced the number of experimental metastases. These experimental data suggest a causal association of secreted cav-1 and prostate cancer growth and progression.
Molecular Cancer Research 10/2009; 7(9):1446-55. · 4.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 66-year-old male was referred to our hospital for evaluation of tumors in his left residual ureter and the lung. He had a history of left nephrectomy due to "malignant renal tumor", performed by a general surgeon at another hospital 16 years ago. Since a definitive diagnosis of the kidney was uncertain, we speculated that the original renal disease was a renal pelvic cancer and had metastasized in the residual ureter and the lung. We performed systemic chemotherapy followed by resection of residual ureter with bladder cuff Pathological examination revealed urothelial carcinoma. However, the lung tumors did not respond to salvage chemotherapy and slowly progressed. Bronchoscopic biopsy was performed 2 years later and histological finding showed clear cell type renal cell carcinoma.
[Show abstract][Hide abstract] ABSTRACT: Purple urine bag syndrome (PUBS) occurs predominantly in chronically catheterized and constipated patients. This syndrome is associated with bacterial urinary tract infections that produce sulfatase or phosphatase. Tryptophan is converted to indole and indigo-producing bacteria have indoxyl phosphatase or sulfatase that can produce indigo (blue) and/or indirubin (red) in patients with urinary tract infection. To further explore the metabolism of these amino acids, we evaluated the serum levels of amino acids in patients with PUBS. A total of 15 patients were enrolled in this case-control study (PUBS-positive case group: 5 patients, PUBS-negative control group: 10 patients). Data from urine tests (pH, sugar, protein, leukocyte counts), renal functions (BUN, creatinine), serum levels of amino acids, and performance status were compared between the two groups. No significant differences were seen between the two groups in urine sugar, protein, leukocyte counts, renal functions, and performance status. The mean urine pH was significantly higher in PUBS patients than in control patients (8.5+/-0.0 vs. 7.3+/-1.16, respectively, p=0.0321), and serum levels of alpha-aminobutyric acid were significantly higher in PUBS patients than in control patients (16.2+/-3.08 vs. 12.4+/-3.20, respectively, p=0.0275). These data suggest that strong alkaline urine acts as an important factor in PUBS, in combination with other facilitating factors.
[Show abstract][Hide abstract] ABSTRACT: Paraganglioma, extra-adrenal pheochromocytomas, are relatively rare in adults, with most arising from para-aortic sympathetic and visceral organs, such as the bladder. Paraganglioma localized at the extravesical retroperitoneal pelvic cavity is extremely rare. We report a case of symptomatic perivesical pheochromocytoma in a 34-year-old man treated by surgical excision. Symptoms related to cathecolamine secretion ceased after surgery, and the patient has remained disease-free for 24 months.