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Find video protocols related to scientific articles indexed in Pubmed.
Effect of Neoadjuvant Chemoradiation on Tumor-infiltrating/associated Lymphocytes in Locally Advanced Rectal Cancers.
Anticancer Res.
PUBLISHED: 11-05-2014
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Lymphocytes and natural killer cells (NK) appear to be important in colorectal cancer. Their role in chemoradiotherapy for rectal cancers is unclear. We evaluated T-lymphocytes (CD3), sub-groups CD4 and CD8, and NK cells (CD56+CD57) in normal and rectal tumor tissues pre- and post-chemoradiotherapy, and investigated their relationship to tumor regression grade, disease-free survival and pathological stage.
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Diffuse melanosis cutis in the setting of BRAF(V) (600) (E) metastatic melanoma.
Int. J. Dermatol.
PUBLISHED: 09-26-2014
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A 79-year-old Caucasian male presented with a 1-week history of diffuse progressive blue-gray discoloration of the skin subsequently found to due to diffuse melanosis cutis (DMC) in the setting of metastatic melanoma. Mutation testing demonstrated BRAF(V) (600E) mutation status, an unexpected finding given his age. He died two weeks after presentation.
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Cutaneous metastasis of prostate carcinoma treated with radiotherapy: a case presentation.
BMC Res Notes
PUBLISHED: 08-08-2014
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Prostate cancer is a commonly diagnosed and treated malignancy, although it rarely presents with cutaneous metastases. In this case presentation, we describe the diagnosis and treatment with radiotherapy of a patient who presented with cutaneous metastases on his chest wall secondary to prostate cancer.
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ANZUP - a new co-operative cancer trials group in genito-urinary oncology.
BJU Int.
PUBLISHED: 07-28-2014
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Shomik Sengupta reports grants from Cancer Australia, during the conduct of the study; and is unremunerated deputy-chair of the bladder cancer subcommittee of the ANZUP Cancer Trials Group Ltd. Peter Grimison reports grants from Cancer Australia, during the conduct of the study; and is unremunerated Chair of the Germ Cell Subcommittee of the ANZUP Cancer Trials Group Ltd. Dickon Hayne reports grants from Cancer Australia, during the conduct of the study; and is unremunerated chair of the bladder cancer subcommittee of the ANZUP Cancer Trials Group Ltd. Scott Williams is unremunerated chair of the prostate cancer subcommittee the ANZUP Cancer Trials Group Ltd. Suzanne Chambers is unremunerated chair of the Quality of Life and Supportive Care Subcommittee of the ANZUP Cancer Trials Group Ltd. Paul DeSouza is unremunerated Chair of the Translational and Correlative Research Subcommittee of the ANZUP Cancer Trials Group Ltd. Martin Stockler reports reports grants from Cancer Australia, during the conduct of the study; Margaret McJannett is an employee of the ANZUP Cancer Trials Group Ltd. Guy Toner reports grants from Cancer Australia, during the conduct of the study; and is unremunerated Deputy-Chair of the Board of ANZUP Cancer Trials Group Ltd Ian Davis reports grants from Cancer Australia, during the conduct of the study; and is unremunerated Chair of the Board of ANZUP Cancer Trials Group Ltd.
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From bench to bedside: immunotherapy for prostate cancer.
Biomed Res Int
PUBLISHED: 06-05-2014
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The mainstay therapeutic strategy for metastatic castrate-resistant prostate cancer (CRPC) continues to be androgen deprivation therapy usually in combination with chemotherapy or androgen receptor targeting therapy in either sequence, or recently approved novel agents such as Radium 223. However, immunotherapy has also emerged as an option for the treatment of this disease following the approval of sipuleucel-T by the FDA in 2010. Immunotherapy is a rational approach for prostate cancer based on a body of evidence suggesting these cancers are inherently immunogenic and, most importantly, that immunological interventions can induce protective antitumour responses. Various forms of immunotherapy are currently being explored clinically, with the most common being cancer vaccines (dendritic-cell, viral, and whole tumour cell-based) and immune checkpoint inhibition. This review will discuss recent clinical developments of immune-based therapies for prostate cancer that have reached the phase III clinical trial stage. A perspective of how immunotherapy could be best employed within current treatment regimes to achieve most clinical benefits is also provided.
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Systemic therapy in neurofibromatosis type 2.
Cancer Treat. Rev.
PUBLISHED: 05-08-2014
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The systemic treatment of patients with neurofibromatosis type 2 associated tumours is challenging, as these patients often have prolonged survival but with the inevitable propensity for their disease to cause symptoms, and no effective therapies other than local treatments such as surgery. Understanding the molecular mechanisms driving NF-2 pathogenesis holds promise for the potential use of targeted therapy. Initial studies of agents such as bevacizumab (angiogenesis inhibitor) and lapatinib (epidermal growth factor and ErbB2 inhibitor) have indicated benefit for selected patients. As the biology of NF-2 is dependent on multiple interlinked downstream signalling pathways, targeting multiple pathways may be more effective than single agents. Phase zero trials, adaptive phase II or small multi-arm trials, are likely the way forward in this rare disease. Ideally, well-tolerated targeted therapy would appear to be the most promising approach for patients with NF-2, given the natural history of this disease.
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Updated Interim Efficacy Analysis and Long-term Safety of Abiraterone Acetate in Metastatic Castration-resistant Prostate Cancer Patients Without Prior Chemotherapy (COU-AA-302).
Eur. Urol.
PUBLISHED: 02-24-2014
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Abiraterone acetate (an androgen biosynthesis inhibitor) plus prednisone is approved for treating patients with metastatic castration-resistant prostate cancer (mCRPC). Study COU-AA-302 evaluated abiraterone acetate plus prednisone versus prednisone alone in mildly symptomatic or asymptomatic patients with progressive mCRPC without prior chemotherapy.
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Outcomes of ethnic minority groups with node-positive, non-metastatic breast cancer in two tertiary referral centers in Sydney, Australia.
PLoS ONE
PUBLISHED: 01-01-2014
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There is a lack of information in ethnic minority groups with regard to presentation and treatment of early node-positive breast cancer. We carried out a retrospective study of patients referred to two tertiary cancer centers in South Western Sydney, both of which serve a high proportion of this ethnic minority population.
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Current and potential treatments for cervical cancer.
Curr Cancer Drug Targets
PUBLISHED: 09-17-2013
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Cervical cancer is the third most common carcinoma in women worldwide. Despite increasing efforts to improve therapy in this disease, a significant proportion of women still die, mostly from recurrent or chemoresistant disease. This review discusses current treatments for early cervical cancer, advanced disease, and recurrent cervical cancer, and covers concurrent chemoradiation, neoadjuvant chemotherapy before surgery and radiation, single agent treatment, combination treatment, platinum-based and non-platinum based therapy. We also discuss promising therapeutics trategies for cervical cancer including targeted therapy, cell-based therapy, combined siRNA and chemotherapy, and immunotherapy.
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Randomized trial of decongestive lymphatic therapy for the treatment of lymphedema in women with breast cancer.
J. Clin. Oncol.
PUBLISHED: 09-16-2013
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Because of its morbidity and chronicity, arm lymphedema remains a concerning complication of breast cancer treatment. Although massage-based decongestive therapy is often recommended, randomized trials have not consistently demonstrated benefit over more conservative measures.
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Pazopanib versus sunitinib in metastatic renal-cell carcinoma.
N. Engl. J. Med.
PUBLISHED: 08-23-2013
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Pazopanib and sunitinib provided a progression-free survival benefit, as compared with placebo or interferon, in previous phase 3 studies involving patients with metastatic renal-cell carcinoma. This phase 3, randomized trial compared the efficacy and safety of pazopanib and sunitinib as first-line therapy.
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Primary treatment of the prostate improves local palliation in men who ultimately develop castrate-resistant prostate cancer.
BJU Int.
PUBLISHED: 07-25-2013
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To determine whether local treatment of primary prostate cancer gives palliative benefit to men who later develop castrate-resistant prostate cancer (CRPC). Local treatments of primary prostate cancer are defined as radical retropubic prostatectomy (RRP) or external beam radiation therapy (EBRT).
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New frontiers in circulating tumor cell analysis - a reference guide for biomolecular profiling towards translational clinical use.
Int. J. Cancer
PUBLISHED: 07-16-2013
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Circulating tumor cells (CTCs) are now routinely isolated from blood and measurement of CTC concentrations appears to correlate well with survival in cancer patients. Interrogation of the molecular profile of CTCs for expression of protein biomarkers, genetic variants and gene expression provides opportunities to use this information to guide personalized treatment, monitor therapy and detect emerging resistance. However, successful application of profiling techniques requires analyses that deliver a reliable and clinically relevant representation of a patients cancer as it changes with time. Here we comprehensively review current knowledge of therapeutically relevant biomarkers in isolated CTCs obtained by fluorescence imaging and genomic profiling approaches. The reviewed data support the notion that molecular profiling of CTCs will provide a reliable representation or surrogate index of tumor burden. Large scale translational trials, many currently in progress, will provide critical data to progress CTC analysis towards wider clinical use in personalized treatment. © 2013 Wiley Periodicals, Inc.
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Imatinib in neurofibromatosis type 2.
BMJ Case Rep
PUBLISHED: 07-11-2013
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A 30-year-old man with a 10-year history of neurofibromatosis type 2 (NF-2) and minimal hearing in his left ear, presented with rapidly progressive disease and risk of total hearing loss. He was started on imatinib and achieved stable disease for 4 months, after which the drug was ceased due to toxicity. He was then treated with bevacizumab for 8 months with a best response of stable disease.
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Phase III, randomized, double-blind, placebo-controlled study of modafinil for fatigue in patients treated with docetaxel-based chemotherapy.
Support Care Cancer
PUBLISHED: 04-21-2013
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Modafinil has been reported to benefit a subgroup of patients suffering severe fatigue while undergoing chemotherapy. Docetaxel is associated with fatigue that may lead to premature therapy withdrawal. We investigated whether modafinil could reduce fatigue during docetaxel chemotherapy.
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Folate conjugation to polymeric micelles via boronic acid ester to deliver platinum drugs to ovarian cancer cell lines.
Biomacromolecules
PUBLISHED: 03-26-2013
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In this study, a novel technique was used for the reversible attachment of folic acid on the surface of polymeric micelles for a tumor-specific drug delivery system. The reversible conjugation is based on the interaction between phenylboronic acid (PBA) and dopamine to form a borate ester. The conjugation is fast and efficient and in vitro experiments via confocal fluorescent microscopy show that the linker is stable in for several hours. Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to synthesize two various sized water-soluble block copolymer of oligoethylene glycol methylether methacylate and methyl acrylic acid (POEGMEMA(35)-b-PMAA(200) and POEGMEMA(26)-b-PMAA(90)). The platinum drug, oxoplatin, was then subsequently attached to the polymer via ester formation leading to platinum loading of 12 wt % as determined by TGA. The platinum-induced amphiphilic block copolymers that consequently led to the formation of micelles of sizes 150 and 20 nm in an aqueous environment with the longer PMAA block forming larger micelles. The small micelles were in addition cross-linked using 1,8-diaminooctane to further stabilize their structure. The targeting ability of folate conjugated polymeric micelles was investigated against two types of tumor cell lines: A549 (-FR) and OVCAR-3 (+FR). The cell line growth inhibitory efficacy of material synthesized was evaluated by using SRB method. The results revealed that folate conjugated micelles showed higher activity in FR + OVCAR-3 cells but not in FR - A549 cells. Similar results were obtained for both small and large micelles without the conjugation of folate. Comparing large and small micelles it can be observed that larger micelles are more efficient, which has been attributed to the lower stability of the smaller micelles. Micelle stabilization via cross-linking could indeed increase the toxicity of the drug carrier.
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Risk factors for erectile dysfunction in a cohort of 108 477 Australian men.
Med. J. Aust.
PUBLISHED: 03-06-2013
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To quantify relationships between erectile dysfunction (ED), ageing and health and lifestyle factors for men aged 45 years and older.
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Bayesian methods for pharmacokinetic/pharmacodynamic modeling of pazopanib-induced increases in blood pressure and transaminases.
J Clin Pharmacol
PUBLISHED: 02-04-2013
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Relationships between plasma pazopanib concentrations and the probability of elevations in blood pressure, a marker of vascular endothelial growth factor receptor inhibition, and alanine aminotransferase (ALT) were investigated with logistic regression models. Data from a Phase I dose-escalation study in cancer patients (n?=?57) were examined to determine the relationship between steady-state trough plasma pazopanib concentrations (C? ) and a clinically significant blood pressure increase, using a Bayesian logistic regression model. Data from 5 monotherapy studies in cancer patients (n?=?344) were pooled to investigate the relationship between C? and maximum ALT???3× the upper limit of normal (ULN), using a Bayesian logistic regression model incorporating an asymptote. Both models were fit using WinBUGS. The median (95% credible interval, CrI) C? at which the probability of a clinically significant increase in blood pressure was 50% (EC50 ) was 12.3??g/mL (6.12, 18.4). The median (95% CrI) EC50 for the maximum probability of ALT???3?×?ULN was 15.4??g/mL (3.8, 41.2) and the median (95% CrI) maximum probability of ALT???3?×?ULN was 21% (14.5, 43.1). Results suggest that dose adjustments could be useful in managing the potential for hepatotoxicity.
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A randomized phase 2 study of paclitaxel and carboplatin with or without conatumumab for first-line treatment of advanced non-small-cell lung cancer.
J Thorac Oncol
PUBLISHED: 02-02-2013
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This study evaluated the efficacy, safety, and pharmacokinetics of conatumumab combined with paclitaxel-carboplatin (PC) as first-line treatment for advanced non-small-cell lung cancer (NSCLC).
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Pazopanib efficacy in renal cell carcinoma: evidence for predictive genetic markers in angiogenesis-related and exposure-related genes.
J. Clin. Oncol.
PUBLISHED: 05-16-2011
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Pazopanib, an oral angiogenesis inhibitor, is approved for the treatment of advanced renal cell carcinoma (RCC). Response to pazopanib monotherapy varies between patients, and no validated biomarkers predictive of treatment outcome have been identified. We tested the hypothesis that this variability is partially dependent on germline genetic variants that may affect pazopanib exposure or angiogenesis pathways.
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Thiol-yne and thiol-ene "click" chemistry as a tool for a variety of platinum drug delivery carriers, from statistical copolymers to crosslinked micelles.
Biomacromolecules
PUBLISHED: 04-25-2011
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Statistical and block copolymers based on poly(2-hydroxyethyl methacrylate) (PHEMA) and poly[oligo(ethylene glycol) methylether methacrylate] (POEGMEMA) were modified with 4-pentenoic anhydride or 4-oxo-4-(prop-2-ynyloxy)butanoic anhydride to generate polymers with pendant vinyl or acetylene, respectively. Subsequent thiol-ene or thiol-yne reaction with thioglycolic acid or 2-mercaptosuccinic acid leads to polymers with carboxylate functionalities, which were conjugated with cisplatin (cis-diamminedichloroplatinum(II) (CDDP)) to generate a drug carrier for Pt-drugs. Only the polymers modified with 2-mercaptosuccinic acid resulted in the formation of soluble well-defined polymers with gel formation being prevented. Due to the hydrophobicity of the drug, the block copolymers took on amphiphilic character leading to micelle formation. The micelles were in addition crosslinked to further stabilize their structure. Pt-containing statistical copolymer, micelles, and crosslinked micelles were then tested regarding their cellular uptake by the A549 lung cancer cell line to show a superior uptake of crosslinked micelles. However, due to the better Pt release of the statistical copolymer, the highest cytotoxicity was observed with this type of polymer architecture.
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Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer.
BMC Clin Pharmacol
PUBLISHED: 02-03-2011
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Phenoxodiol is a novel isoflavone currently being studied in clinical trials for the treatment of cancer. This study reports the pharmacokinetics of phenoxodiol in patients with cancer.
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Ras Isoprenylation and pAkt Inhibition by Zoledronic Acid and Fluvastatin Enhances Paclitaxel Activity in T24 Bladder Cancer Cells.
Cancers (Basel)
PUBLISHED: 01-30-2011
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Background: Bisphosphonates interfere with the mevalonate pathway and inhibit the prenylation of small GTP-binding proteins such as ras and rap. We hypothesized that zoledronic acid would synergistically inhibit T24 bladder cancer cell growth in combination with fluvastatin and paclitaxel. Methods: Increasing doses of fluvastatin, zoledronic acid, and paclitaxel were investigated as single agents and in combination, and synergistic interactions were evaluated by the Chou-Talalay method. Western blots were used to assess effects on signal transduction pathways. Results: Growth of T24 was significantly inhibited with IC50 values of 2.67 ± 0.61 mM for fluvastatin and 5.35 ± 1.35 mM for zoledronic acid after 72 hours treatment. Geranylgeranyl pyrophosphate and farnesyl pyrophosphate was able to block, in part, this inhibitory activity. The combinations of zoledronic acid and paclitaxel, zoledronic acid and fluvastatin, and fluvastatin and paclitaxel were all synergistic. Both fluvastatin and zoledronic acid inhibited Ras and Rap prenylation, and the phosphorylation of ERK1/2 and AKT. The degree of inhibition of phosphorylation of these key signaling transduction pathways appears to closely correlate with their synergistic interactions. Conclusions: Zoledronic acid enhances fluvastatin and paclitaxel activity against T24 in a synergistic manner and this is mediated largely by inhibition of both the Ras/Raf/MEK/ERK and PI3K/AKT signaling pathways via isoprenylation inhibition.
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The pharmacological advantage of prolonged dose rate gemcitabine is restricted to patients with variant alleles of cytidine deaminase c.79A>C.
Asia Pac J Clin Oncol
PUBLISHED: 12-30-2010
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Controversy exists over the optimal dosing for the nucleoside analogue gemcitabine. A pharmacological advantage is achieved by prolonging infusion times but evidence for a clinical benefit has been conflicting. We hypothesized that polymorphisms in genes involved in gemcitabine accumulation, particularly the cytidine deaminase CDA c.79A>C, may influence the optimal dosing regimen in individual patients.
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A phase II trial of weekly i.v. KW-2170 in advanced castrate-resistant prostate cancer.
Asia Pac J Clin Oncol
PUBLISHED: 11-03-2010
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KW-2170 is a novel pyrazoloacridone derivative that intercalates nucleic acids. It has promising in vitro properties against prostate and other cancers and is active in vivo against doxorubicin-resistant cell lines. We wished to investigate its activity and toxicity profile in this Phase II trial in androgen independent prostate cancer.
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Conditions causing gemcitabine crystallization.
J Oncol Pharm Pract
PUBLISHED: 09-21-2010
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Intravesical delivery of chemotherapy agents is used very commonly for the treatment of superficial bladder cancer. We recently completed a phase II study of intravesical gemcitabine in which an alkaline adjusted gemcitabine preparation was used initially, based on very early phase I studies. However, crystallization was noted in some of the pre-prepared syringes, which prompted us to investigate the conditions under which gemcitabine crystallized.
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Core-cross-linked micelles synthesized by clicking bifunctional Pt(IV) anticancer drugs to isocyanates.
Biomacromolecules
PUBLISHED: 09-14-2010
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Most low molecular weight platinum-based anticancer drugs have a short circulation time in the bloodstream. One of the potential strategies to improve the targeted delivery of cisplatin and prolong its circulation is via the use of nanocarriers. An improved drug delivery system was developed via reversible addition-fragmentation chain transfer (RAFT) polymerization. In a one-pot reaction, the incorporation of anticancer drug and core cross-linking was simultaneously carried out by using the highly effective reaction of isocyanate groups in the core of the polymeric micelles poly(oligo(ethylene glycol) methyl ether methacrylate)-block-poly(styrene-co-3-isopropenyl-?,?-dimethylbenzyl isocyanate) (POEGMA-block-P(STY-co-TMI)) with amine groups in the prepared platinum(IV) drug. The micelles with platinum(IV) incorporated with a size of 36 nm were very stable in water. In a reductive environment, in this study simulated using ascorbate, the drug was released at a slow rate of 82% in 22 days and at the same time the cross-linked micelle broke down into free block copolymers as evidenced using inductively coupled plasma-mass spectrometer (ICP-MS), size exclusion chromatography (SEC), and dynamic light scattering (DLS). The in vitro study also revealed the promising antitumor activity of prepared platinum(IV) drugs encapsulated into the micelle structure.
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Clinical pharmacology of isoflavones and its relevance for potential prevention of prostate cancer.
Nutr. Rev.
PUBLISHED: 08-28-2010
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Isoflavones are phytoestrogens that have pleiotropic effects in a wide variety of cancer cell lines. Many of these biological effects involve key components of signal transduction pathways within cancer cells, including prostate cancer cells. Epidemiological studies have raised the hypothesis that isoflavones may play an important role in the prevention and modulation of prostate cancer growth. Since randomized phase III trials of isoflavones in prostate cancer prevention are currently lacking, the best evidence for this concept is presently provided by case control studies. However, in vitro data are much more convincing in regard to the activity of a number of isoflavones, and have led to the development of genistein and phenoxodiol in the clinic as potential treatments for cancer. In addition, the potential activity of isoflavones in combination with cytotoxics or radiotherapy warrants further investigation. This review focuses on the clinical pharmacology of isoflavones and its relevance to their development for use in the prevention of prostate cancer, and it evaluates some of the conflicting data in the literature.
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Emerging roles for phospholipase A2 enzymes in cancer.
Biochimie
PUBLISHED: 03-24-2010
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Phospholipase A(2) (PLA(2)) enzymes (EC3.1.4.4) regulate the release of biologically active fatty acids and lysophospholipids from membrane phospholipid pools. These lipids are also substrates for intracellular biochemical pathways that generate potent autocrine and paracrine lipid mediators such as the eicosanoids and platelet activating factor. These factors, in turn, regulate cell proliferation, survival, differentiation, motility, tissue vascularisation, and immune surveillance in virtually all tissues, functions that are subverted by cancer cells for tumour growth and metastasis. Thus the relevance of PLA(2)-dependent pathways to the genesis and progression of cancer has been of interest since their discovery and with recent technological advances, their role in tumourigenesis has become more tractable experimentally. Limited human genetic studies have not yet identified PLA(2) enzymes as classical mutated oncogenes or tumour suppressor genes. However, there is strong evidence that of the 22 identified human PLA(2) enzymes, ten of which have been studied in cancer to date, most are aberrantly expressed in a proportion of tumours derived from diverse organs. Correlative and functional studies implicate the expression of some secreted enzymes (sPLA(2)s), particularly the best studied enzyme Group IIA sPLA(2) in either tumour promotion or inhibition, depending on the organ involved and the biochemical microenvironment of tumours. As in immune-mediated inflammatory pathologies, genetic deletion studies in mice, supported by limited studies with human cells and tissues, have identified an important role for Group IVA PLA(2) in regulating certain cancers. Pharmacological intervention studies in prostate cancer suggest that hGIIA-dependent tumour growth is dependent on indirect regulation of Group IVA PLA(2). Group VI calcium-independent PLA(2) enzymes have also been recently implicated in tumourigenesis with in vitro studies suggesting multiple possible roles for these enzymes. Though apparently complex, further characterization of the regulatory relationships amongst PLA(2) enzymes, lipid mediator biosynthetic enzymes and the lipid mediators they produce during tumour progression is required to define the biochemical context in which the enzymes modulate cancer growth and development.
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Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma.
J. Clin. Oncol.
PUBLISHED: 12-14-2009
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Inactivation of the von Hippel-Lindau gene in clear-cell renal cell carcinomas (RCC) leads to overexpression of hypoxia inducible factor, a transcription factor regulating vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) gene expression. Pazopanib, an angiogenesis inhibitor targeting VEGF receptor, PDGF receptor, and c-KIT, was evaluated in patients with RCC.
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Analysis of PTEN and HIF-1alpha and correlation with efficacy in patients with advanced renal cell carcinoma treated with temsirolimus versus interferon-alpha.
Cancer
PUBLISHED: 06-16-2009
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Exploratory subgroup analyses from the phase 3 global advanced renal cell carcinoma (ARCC) trial were conducted to determine if baseline levels of the tumor molecular markers PTEN and HIF1 alpha correlated with efficacy in patients treated with temsirolimus (Torisel) versus interferon-alpha (IFN).
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Role of the Akt pathway in prostate cancer.
Curr Cancer Drug Targets
PUBLISHED: 03-12-2009
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The Akt pathway, or more accurately, network, has assumed increasing importance with the understanding that it represents a key role in cancer cell survival and proliferation. Intense efforts to target proteins and enzymes within this pathway with highly selective compounds have led to the development of diverse agents now in Phase I-III clinical trials. Moreover, the notion that exploitation of multiple "druggable" targets simultaneously or in the appropriate sequence may provide better anti-tumour effects than single drugs hold promise that chemoresistance may be overcome, at least in part. This paper reviews important aspects of the Akt network, with a particular focus on prostate cancer biology.
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Effect of temsirolimus versus interferon-alpha on outcome of patients with advanced renal cell carcinoma of different tumor histologies.
Med. Oncol.
PUBLISHED: 01-27-2009
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Purpose Exploratory subgroup analyses from the phase 3 global advanced renal cell carcinoma (ARCC) trial were conducted to assess the influence of tumor histology on outcome of patients treated with temsirolimus (Torisel) or interferon-alpha (IFN). Patients and methods Patients with ARCC including clear cell and other types such as papillary and chromophobe histologies received either IFN (3 million units [MU] subcutaneously three times weekly, escalating to 18 MU) or temsirolimus (25 mg intravenously weekly). Results Approximately 80% of patients had clear cell and 20% of patients had other histologies, the majority of which were papillary. Patients with clear cell and other RCC histologies, treated with temsirolimus, demonstrated comparable median overall and progression-free survival. In contrast, patients with other RCC histologies, treated with IFN, demonstrated shorter median overall and progression-free survival than patients with clear cell RCC. Hazard ratios for death for treatment with temsirolimus versus IFN were less than 1 for patients regardless of tumor histology. For patients treated with temsirolimus, 59% with clear cell and 68% with other RCC histologies experienced tumor reductions. For patients treated with IFN, 35% with clear cell and 14% with other RCC histologies had tumor reductions. However, temsirolimus did not appear to improve the objective response rate compared to IFN. Temsirolimus resulted in a superior clinical benefit rate compared with IFN, regardless of tumor histology. Conclusion Temsirolimus appears to be efficacious in patients with clear cell and non-clear cell histologies and can, therefore, be used for the treatment of all types of RCC.
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Efficacy of erlotinib in patients with advanced non-small-cell lung cancer (NSCLC): analysis of the Australian subpopulation of the TRUST study.
Asia Pac J Clin Oncol
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The efficacy of erlotinib (Tarceva, Roche Products, Dee Why, Australia) has been demonstrated in patients with advanced non-small-cell lung cancer (NSCLC). Tarceva lung cancer survival treatment (TRUST) is an open-label, single-arm, phase IV global trial which investigated erlotinib in advanced NSCLC patients who had failed prior therapy or were unsuitable for chemo/radiotherapy. The aim of this analysis was to report the safety and efficacy of erlotinib in the Australian patient subpopulation.
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Cancer-related fatigue in women with breast cancer: outcomes of a 5-year prospective cohort study.
J. Clin. Oncol.
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Prolonged and disabling fatigue is prevalent after cancer treatment, but the early natural history of cancer-related fatigue (CRF) has not been systematically examined to document consistent presence of symptoms. Hence, relationships to cancer, surgery, and adjuvant therapy are unclear.
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Increase in cholesterol predicts survival advantage in renal cell carcinoma patients treated with temsirolimus.
Clin. Cancer Res.
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Temsirolimus is an effective treatment for renal cell carcinoma. It is associated with increases in serum cholesterol, triglyceride, and glucose. We investigated whether changes of these biomarkers could predict its efficacy.
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Block copolymer micelles with pendant bifunctional chelator for platinum drugs: effect of spacer length on the viability of tumor cells.
Biomacromolecules
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Three monomers with 1,3-dicarboxylate functional groups but varying spacer lengths were synthesized via carbon Michael addition using malonate esters and ethylene- (MAETC), butylene- (MABTC), and hexylene (MAHTC) glycol dimethacrylate, respectively. Poly[oligo-(ethylene glycol) methylether methacrylate] (POEGMEMA) was prepared in the presence of a RAFT (reversible addition-fragmentation chain transfer) agent, followed by chain extension with the prepared monomers to generate three different block copolymers (BP-E80, BP-B82, and BP-H79) with similar numbers of repeating units, but various spacer lengths as distinguishing features. Conjugation with platinum drugs created macromolecular platinum drugs resembling carboplatin. The amphiphilic natures of these Pt-containing block copolymers led to the formation micelles in solution. The rate of drug release of all micelles was similar, but a noticeable difference was the increasing stability of the micelle against dissociation with increasing spacer length. The platinum conjugated polymer showed high activity against A549, OVCAR3, and SKOV3 cancer cell lines exceeding the activity of carboplatin, but only the micelle based on the longest spacer had IC(50) values as low as cisplatin. Cellular uptake studies identified a better micelle uptake with increasing micelle stability as a possible reason for lower IC(50) values. The clonogenic assay revealed that micelles loaded with platinum drugs, in contrast to low molecular weight carboplatin, have not only better activity within the frame of a 72 h cell viability study, but also display a longer lasting effect by preventing the colony formation A549 for more than 10 days.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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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.