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Find video protocols related to scientific articles indexed in Pubmed.
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Diagnostic performance and safety of a three-dimensional 14-core systematic biopsy method.
BJU Int.
PUBLISHED: 04-16-2014
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To investigate the diagnostic performance and safety of a three-dimensional 14-core biopsy (3D14PBx) method, which is a combination of the transrectal six-core and transperineal eight-core biopsy methods.
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The HSP90 Inhibitor Ganetespib Synergizes with the MET Kinase Inhibitor Crizotinib in both Crizotinib-Sensitive and -Resistant MET-Driven Tumor Models.
Cancer Res.
PUBLISHED: 10-11-2013
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The proto-oncogene MET is aberrantly activated via overexpression or mutation in numerous cancers, making it a prime anticancer molecular target. However, the clinical success of MET-directed tyrosine kinase inhibitors (TKI) has been limited due, in part, to mutations in the MET kinase domain that confer therapeutic resistance. Circumventing this problem remains a key challenge to improving durable responses in patients receiving MET-targeted therapy. MET is an HSP90-dependent kinase, and in this report we show that HSP90 preferentially interacts with and stabilizes activated MET, regardless of whether the activation is ligand-dependent or is a consequence of kinase domain mutation. In contrast, many MET-TKI show a preference for the inactive form of the kinase, and activating mutations in MET can confer resistance. Combining the HSP90 inhibitor ganetespib with the MET-TKI crizotinib achieves synergistic inhibition of MET, its downstream signaling pathways, and tumor growth in both TKI-sensitive and -resistant MET-driven tumor models. These data suggest that inclusion of an HSP90 inhibitor can partially restore TKI sensitivity to previously resistant MET mutants, and they provide the foundation for clinical evaluation of this therapeutic combination in patients with MET-driven cancers. Cancer Res; 73(23); 7022-33. ©2013 AACR.
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Diabetes mellitus with obesity is a predictor of recurrence in patients with non-metastatic renal cell carcinoma.
Jpn. J. Clin. Oncol.
PUBLISHED: 05-31-2013
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To investigate the associations of diabetes mellitus with recurrence and prognosis after surgery for non-metastatic renal cell carcinoma and the effect modification of obesity on the above relationships.
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Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-05-2013
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TRAP1 (TNF receptor-associated protein), a member of the HSP90 chaperone family, is found predominantly in mitochondria. TRAP1 is broadly considered to be an anticancer molecular target. However, current inhibitors cannot distinguish between HSP90 and TRAP1, making their utility as probes of TRAP1-specific function questionable. Some cancers express less TRAP1 than do their normal tissue counterparts, suggesting that TRAP1 function in mitochondria of normal and transformed cells is more complex than previously appreciated. We have used TRAP1-null cells and transient TRAP1 silencing/overexpression to show that TRAP1 regulates a metabolic switch between oxidative phosphorylation and aerobic glycolysis in immortalized mouse fibroblasts and in human tumor cells. TRAP1-deficiency promotes an increase in mitochondrial respiration and fatty acid oxidation, and in cellular accumulation of tricarboxylic acid cycle intermediates, ATP and reactive oxygen species. At the same time, glucose metabolism is suppressed. TRAP1-deficient cells also display strikingly enhanced invasiveness. TRAP1 interaction with and regulation of mitochondrial c-Src provide a mechanistic basis for these phenotypes. Taken together with the observation that TRAP1 expression is inversely correlated with tumor grade in several cancers, these data suggest that, in some settings, this mitochondrial molecular chaperone may act as a tumor suppressor.
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Successful reduction of hospital-acquired methicillin-resistant Staphylococcus aureus in a urology ward: a 10-year study.
BMC Urol
PUBLISHED: 02-16-2013
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To eradicate hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) using a stepwise infection control strategy that includes an avoidance of antimicrobial prophylaxis (AMP) based on surgical wound classification and an improvement in operative procedures in gasless single-port urologic surgery.
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Zoledronic acid sensitizes renal cell carcinoma cells to radiation by downregulating STAT1.
PLoS ONE
PUBLISHED: 01-01-2013
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Zoledronic acid (ZOL), a third-generation bisphosphonate that strongly inhibits osteoclast activity, is widely used for the treatment of bone metastasis from a variety of malignancies, including renal cell carcinoma (RCC). We previously reported that zoledronic acid (ZOL) clinically potentiates antitumor effects of radiotherapy (RT) on bone metastases from RCC. To date, however, it remains unknown whether ZOL radiosensitizes RCC and if it does, how. Here, we demonstrated that ZOL directly radiosensitizes RCC cells independent of osteoclast activity by potentiating the caspase-3-mediated apoptosis pathway. The radiosensitization by ZOL was observed in 786-O, A-498, and ACHN cells but not in Caki-1 cells. As its underlying molecular mechanism, we found that the signal transducer and activator of transcription 1 (STAT1) plays a key role. The three RCC cell lines, in which ZOL exerted a radiosensitizing effect, expressed STAT1 abundantly but Caki-1 cells did not. ZOL downregulated endogenous STAT1 expression in 786-O, A-498, and ACHN cells by a post-transcriptional modification. We confirmed that knockdown of endogenous STAT1 by siRNA sensitized 786-O cells to RT equivalently to ZOL, and that introduction of exogenous STAT1 rendered Caki-1 cells more RT-resistant. This is the first study to clarify the molecular mechanism by which ZOL directly radiosensitizes tumor cells. Because tumor cells commonly overexpress STAT1 and ZOL reportedly radiosensitizes various types of tumor cells, ZOL warrants further clinical and translational studies as a potent radiosensitizer against RT-resistant tumors overexpressing STAT1.
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Low-dose Hsp90 inhibitors tumor-selectively sensitize bladder cancer cells to chemoradiotherapy.
Cell Cycle
PUBLISHED: 12-15-2011
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Although radical cystectomy with urinary diversion is the standard treatment for muscle-invasive bladder cancer (MIBC), loss of native bladder frequently impairs patients quality of life (QOL). Bladder-sparing approach incorporating chemoradiotherapy (CRT) improves QOL while not compromising survival outcomes in MIBC patients. In this approach, complete response to induction CRT is a prerequisite for bladder preservation and favorable oncological outcomes. We investigated a strategy to potentiate CRT response of bladder cancer cells by using Hsp90 inhibitors in preclinical models. Hsp90 inhibitors at low concentrations, which did not exert cytocidal effects but inactivated key anti-apoptotic proteins including erbB2, Akt, and NF-?B, efficiently sensitized bladder cancer cells (T24, 5637 and UM-UC-3 cells) to in vitro CRT by enhancing apoptosis. Importantly, the sensitizing effects were not observed in primarily cultured normal human urothelial cells. We also showed that CRT induces accumulation of nuclear phospho-Akt, which antagonizes apoptosis, and that Hsp90 inhibitors block the cellular process. Hsp90 inhibition sensitized bladder cancer cells to in vitro CRT more effectively than sole or combined inhibition of erbB2 and Akt. In mice UM-UC-3 tumor xenografts model, Hsp90 inhibitors successfully potentiated anti-tumor activity of CRT. These results encourage clinical trials of Hsp90 inhibitors to overcome CRT resistance in patients with MIBC.
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[Successful treatment with multidisciplinary therapy including low-dose chemoradiotherapy against metastatic recurrences of small cell carcinoma of the renal pelvis: a case report].
Nippon Hinyokika Gakkai Zasshi
PUBLISHED: 10-04-2011
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Primary small cell carcinoma of the renal pelvis is a rare and aggressive disease; reportedly, a mean survival is only 8 months. A 78 year-old woman with chronic kidney disease was referred to our hospital complaining of asymptomatic gross hematoturia. On imaging studies and voided urine cytology, diagnosis of right renal pelvic cancer (cT2N0M0) was made. She underwent total nephroureterectomy. Pathological diagnosis was small cell carcinoma, infiltrating into the renal parenchyma, with lymphovascular invasion. Post-operatively, hemodialysis was introduced. Five months after the operation, new lesions developed in the right adrenal gland, aortocaval lymph nodes and subcutaneous layer of the right back. The subcutaneous mass was surgically removed and low-dose chemoradiotherapy (sigma 45 Gy/25 Fr/32 d + cisplatin 10 mg/d for 2 d x 2) was given to the other lesions. Although the lesions regressed to CR, new small masses emerged in the muscle layers of the right flank 14 months after total nephroureterectomy. Low-dose chemoradiotherapy (sigma 40 Gy/20 Fr/29 d + cisplatin 10 mg/d for 2 d x 2) to these lesions successfully brought CR. She is alive without any evidence of disease at 3 years after total nephroureterectomy.
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ErbB2 and NF?B overexpression as predictors of chemoradiation resistance and putative targets to overcome resistance in muscle-invasive bladder cancer.
PLoS ONE
PUBLISHED: 09-27-2011
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Radical cystectomy for muscle-invasive bladder cancer (MIBC) patients frequently impairs their quality of life (QOL) due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR) to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NF?B, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS) were investigated. Of the 35 patients, 11 (31%) achieved pathological CR, while tumors in the remaining 24 patients (69%) were chemoradiation-resistant. Multivariate analysis identified erbB2 and NF?B overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P?=?0.014), 15.4 (P?=?0.024) and 14.3 (P?=?0.038). The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NF?B, but only 11.1% for those negative for both (P <0.0001). The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NF?B was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P?=?0.056) along with chemoradiation resistance (P?=?0.003) and hydronephrosis (P?=?0.018). The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with chemoradiation-resistant disease was 61% (P?=?0.018). Thus, erbB2 and NF?B overexpression are relevant to chemoradiation resistance and are putative targets aimed at overcoming chemoradiation resistance in MIBC.
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Potential role of Hsp90 inhibitors in overcoming cisplatin resistance of bladder cancer-initiating cells.
Int. J. Cancer
PUBLISHED: 05-12-2011
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For metastatic bladder cancer patients, systemic cisplatin (CDDP)-based combination chemotherapy is the first-line choice of treatment. Although up to 70% of advanced bladder cancer patients initially show good tumor response to this form of combination chemotherapy, over 90% of good responders relapse and eventually die of the disease. According to the cancer stem cell theory, this phenomenon is attributable to the re-growth of bladder cancer-initiating cells (BCICs) that have survived chemotherapy. In this study, the authors have isolated BCICs from cultured human bladder cancer cells to analyze their sensitivity to CDDP and to investigate whether heat-shock protein 90 (Hsp90) inhibitors potentiate the cytotoxicity of CDDP on BCICs. First, the authors have confirmed that a CD44+ subpopulation of 5637 cells met the requirements to be considered tumor-initiating cells. These BCICs were more resistant to CDDP and exhibited more activity in the Akt and ERK oncogenic signaling pathways when compared with their CD44- counterparts. The Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), which simultaneously inactivated both Akt and ERK signaling at noncytocidal concentrations, synergistically potentiated the cytotoxicity of CDDP against BCICs by enhancing CDDP-induced apoptosis in vitro. The potentiating effect of 17-DMAG was more effective than a combination of the two inhibitors specific for the Akt and ERK pathways. Finally, the authors have confirmed that, though human BCIC xenografts exhibited resistance to a single administration of CDDP and the Hsp90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), 17-AAG sensitized them to CDDP in a mouse model. These data encourage clinical trials of Hsp90 inhibitors as they may improve therapeutic outcomes of CDDP-based combination chemotherapy against advanced bladder cancer.
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Young age as favorable prognostic factor for cancer-specific survival in localized renal cell carcinoma.
Urology
PUBLISHED: 01-22-2011
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To evaluate the prognostic effect of age in patients with localized renal cell carcinoma (RCC) and investigate the incidence of Xp11 translocation RCC in young patients who developed recurrence.
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[Successful long-term management of hepatic and lymph nodes metastases of ureteral cancer by multimodal treatment including radiofrequency ablation].
Nippon Hinyokika Gakkai Zasshi
PUBLISHED: 12-24-2010
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A 56-year-old man presented with asymptomatic gross hematuria. Computed tomography (CT) scan revealed right hydronephrosis and a slightly enhanced invasive tumor in the right lower ureter, providing a diagnosis of ureteral cancer stage cT3NOM0. The patient underwent minimum incision endoscopic nephrouretectomy, and pathological examination of the resected specimen revealed urothelial carcinoma and squamous cell carcinoma with metastases to right obturator lymph nodes (pT3pN2). Ten months later, CT scan of the abdomen revealed two hepatic metastases. After three courses of combination chemotherapy consisting of gemcitabine and cisplatin (GC), one tumor completely disappeared and another achieved a partial response. The patient underwent radiofrequency ablation (RFA) for the residual followed by GC chemotherapy. However, eighteen months later, CT scan of the abdomen revealed two metastatic foci in other hepatic lesion. The patient underwent RFA again followed by GC chemotherapy and then all hepatic metastases have not revealed enlargement. More than three years after surgery, the patient has achieved a high quality of life.
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Phase-II trial of combination treatment of interferon-?, cimetidine, cyclooxygenase-2 inhibitor and renin-angiotensin-system inhibitor (I-CCA therapy) for advanced renal cell carcinoma.
Cancer Sci.
PUBLISHED: 10-26-2010
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We have recently reported favorable responses to a combination treatment comprising cimetidine, a cyclooxygenase-2 inhibitor and a renin-angiotensin-system inhibitor in metastatic renal cell carcinoma (RCC). In view of the potential synergistic effects of these three agents and interferon-? (I-CCA therapy), we conducted a phase-II trial to examine the efficacy and toxicity of I-CCA as first-line treatment. Fifty-one patients with advanced RCC received natural interferon-? (3-6 million U thrice/week) and cimetidine (800 mg), cyclooxygenase-2 inhibitor meloxicam (10 mg), and renin-angiotensin-system inhibitor candesartan (4 mg) or perindopril (4 mg) orally daily. Memorial Sloan-Kettering Cancer Center prognostic categories were favorable, intermediate and poor in 10 (20%), 31 (61%) and 10 (20%) patients, respectively. The primary end-point was the objective response rate (ORR) and the secondary end-points included clinical benefit, progression-free survival (PFS), overall survival (OS) and safety. Median follow-up was 19 months. Complete response (CR) was observed in four patients (8%) and partial response in seven (14%), yielding an ORR of 22%. None of the four patients who achieved CR relapsed during the 16- to 81-month follow up. The ORR were 17% in the favorable- or intermediate-risk group and 40% in the poor-risk group. The other 24 patients (45%) had stable disease for at least 6 months, resulting in a clinical benefit rate of 67%. The median PFS and OS were 12 and 30 months, respectively. Grade 3/4 toxicities were never observed. The I-CCA therapy, providing favorable responses and low toxicity profiles, is worthy of further consideration as a first-line therapy for metastatic RCC.
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Impact of C-reactive protein kinetics on survival of patients with metastatic renal cell carcinoma.
Eur. Urol.
PUBLISHED: 10-27-2009
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Pretreatment C-reactive protein (CRP) level has been shown to be prognostic for metastatic renal cell carcinoma (mRCC).
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Antimicrobial prophylaxis is not necessary in clean category minimally invasive surgery for renal and adrenal tumors: a prospective study of 373 consecutive patients.
Urology
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To assess the feasibility of the nonuse of antimicrobial prophylaxis (AMP) on the incidence of infectious complications after clean category minimally invasive surgery for renal and adrenal tumors.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.