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Find video protocols related to scientific articles indexed in Pubmed.
Gynecologic Cancer InterGroup (GCIG) Consensus Review for Mucinous Ovarian Carcinoma.
Int. J. Gynecol. Cancer
PUBLISHED: 10-25-2014
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Mucinous carcinomas of the ovary can be primary or metastatic in origin. Improvements in the pathological diagnosis have increased the ability to distinguish between primary and metastatic ovarian cancers and shown that primary mucinous carcinomas are a rare subtype of ovarian cancer. Most tumors are diagnosed at an early stage, and the prognosis after surgery is good. Advanced or recurrent mucinous carcinoma of the ovary responds poorly to current cytotoxic treatments, and the prognosis is poor. Here, we review the guidelines for surgery and the results of treatment of advanced and recurrent disease. Chemotherapy with platinum and paclitaxel is currently used to treat advanced disease, but the effect of these drugs is modest, and new treatments are needed.
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Gynecologic Cancer InterGroup (GCIG) Consensus Review for Squamous Cell Carcinoma of the Ovary.
Int. J. Gynecol. Cancer
PUBLISHED: 08-16-2014
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Squamous cell carcinoma of the ovary is a rare complication of mature cystic teratoma. The epidemiology, pathology, diagnosis, and management of this rare tumor are reviewed. Clinical characteristics, preoperative imaging, and tumor markers may help to predict malignancy preoperatively. Complete cytoreduction should be the aim of surgery. The prognosis for stage 1A disease is good, but for women with advanced or recurrent disease, it is very poor and has not improved in recent years. At present, there are insufficient data to provide clear guidance on the optimal management strategy for advanced disease, and there is a need to gain an understanding of the biology and to develop novel effective therapies. This will require coordinated international collaboration.
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Drug safety evaluation of sorafenib for treatment of solid tumors: consequences for the risk assessment and management of cancer patients.
Expert Opin Drug Saf
PUBLISHED: 04-03-2014
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Sorafenib is a multi-tyrosine kinase inhibitor (TKI). Considerable clinical experience has been accumulated since its first Phase III clinical trial in metastatic renal cancer patients in 2007. The management of its early acute toxicity in fit patients is well known. The management of prolonged treatment becomes the new challenge.
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Association between high antitumor activity of oxaliplatin and cyclophosphamide and constitutional GSTM1 homozygous deletion in an advanced ovarian cancer patient.
Chemotherapy
PUBLISHED: 01-24-2014
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Although the efficiency of oxaliplatin in patients with advanced ovarian cancer has been demonstrated, it is not commonly used. In cells, oxaliplatin is metabolized by the enzymes belonging to the glutathione-S-transferase (GST) family.
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Treatment of ovarian anaplastic ependymoma by an aromatase inhibitor.
Obstet Gynecol
PUBLISHED: 01-14-2014
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Histopathologic diagnosis and treatment of ovarian anaplastic ependymoma are challenging.
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Phase I study of elisidepsin (Irvalec®) in combination with carboplatin or gemcitabine in patients with advanced malignancies.
Invest New Drugs
PUBLISHED: 01-07-2014
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To determine the maximum tolerated dose and the recommended dose (RD) for phase II trials of elisidepsin (Irvalec®) in combination with carboplatin or gemcitabine.
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Nutritional status is superior to the ECOG performance status in predicting the dose-intensity of the GEMOX chemotherapy regimen in patients with advanced cancer.
Nutr Cancer
PUBLISHED: 10-07-2013
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The increasing number of unfit patients calls for better risk assessment prior to initiating anti-tumor treatment. This is a major concern in the prevention and reduction of treatment-related complications. The aim of our study was to evaluate the nutritional status for the risk assessment of patients qualifying to receive the gemcitabine and oxaliplatin (GEMOX) regimen. This single-center, retrospective study examined baseline clinical and biological characteristics in a cohort of 165 unselected, consecutive cancer patients receiving GEMOX. Malnutrition was defined as either body mass index (BMI) <18.5 kg/m(2), body weight loss >10% over 3 mo, or albuminemia <35 g/L. A total of 165 patients (median age 61 yr, PS 0-1: 71%) were studied. Malnutrition was seen in 43% of PS 0-1 patients, vs. 60% of PS 2 and 66% of PS 3 patients (P > 0.05). Median relative dose-intensity was 0.90 (0.17-1.04). GEMOX dose-intensity correlated negatively with loss of baseline weight (r = -0.24, P < 0.02). In patients who did not complete more than 2 cycles of chemotherapy, median PS (P < 0.01), mean C-reactive protein (CRP; P < 0.01), and mean albuminemia (P < 0.05) were, respectively, significantly higher, higher, and lower. Malnutrition is associated with a high risk of early discontinuance of treatment. Systematic basal evaluation of the nutritional status, including albuminemia and BMI, is recommended.
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A defective Krab-domain zinc-finger transcription factor contributes to altered myogenesis in myotonic dystrophy type 1.
Hum. Mol. Genet.
PUBLISHED: 08-06-2013
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Myotonic dystrophy type 1 (DM1) is an RNA-mediated disorder caused by a non-coding CTG repeat expansion that, in particular, provokes functional alteration of CUG-binding proteins. As a consequence, several genes with misregulated alternative splicing have been linked to clinical symptoms. In our search for additional molecular mechanisms that would trigger functional defects in DM1, we took advantage of mutant gene-carrying human embryonic stem cell lines to identify differentially expressed genes. Among the different genes found to be misregulated by DM1 mutation, one strongly downregulated gene encodes a transcription factor, ZNF37A. In this paper, we show that this defect in expression, which derives from a loss of RNA stability, is controlled by the RNA-binding protein, CUGBP1, and is associated with impaired myogenesis-a functional defect reminiscent of that observed in DM1. Loss of the ZNF37A protein results in changes in the expression of the subunit ?1 of the receptor for the interleukin 13. This suggests that the pathological molecular mechanisms linking ZNF37A and myogenesis may involve the signaling pathway that is known to promote myoblast recruitment during development and regeneration.
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A new strategy to target regulatory T cells in solid tumors.
Oncoimmunology
PUBLISHED: 06-27-2013
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The depletion of regulatory T cells (Tregs) is a promising therapeutic strategy to enhance antitumor immune responses. Our recent findings indicate that low doses of arsenic trioxide can delay tumor growth in murine models of colon and breast cancer by depleting Tregs through oxidative and nitrosative bursts.
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Impact of a second opinion using expression and molecular analysis of FOXL2 for sex cord-stromal tumors. A study of the GINECO group & the TMRO network.
Gynecol. Oncol.
PUBLISHED: 06-25-2013
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Ovarian sex cord-stromal tumors (SCSTs) are rare and their diagnosis is often difficult to establish. Recently, immunostaining and molecular analysis for Forkhead box L2 (FOXL2) have been developed in this pathology. This study aims to assess the benefit of an algorithm incorporating these new tools for a better diagnosis and classification of SCSTs METHODS: Seventy-two tumors with a potential diagnosis of SCSTs were addressed by 37 different pathologists to one French rare ovarian tumor expert center, member of the Rare Malignant Ovarian Tumor network (TMRO). Then a "second opinion" (SO) through an algorithm incorporating immunostaining (IHC) and molecular analysis of FOXL2 was performed for all these cases. This algorithm was then validated by all pathologists of the TMRO network.
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mTOR-dependent proliferation defect in human ES-derived neural stem cells affected by myotonic dystrophy type 1.
J. Cell. Sci.
PUBLISHED: 02-26-2013
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Patients with myotonic dystrophy type 1 exhibit a diversity of symptoms that affect many different organs. Among these are cognitive dysfunctions, the origin of which has remained elusive, partly because of the difficulty in accessing neural cells. Here, we have taken advantage of pluripotent stem cell lines derived from embryos identified during a pre-implantation genetic diagnosis for mutant-gene carriers, to produce early neuronal cells. Functional characterization of these cells revealed reduced proliferative capacity and increased autophagy linked to mTOR signaling pathway alterations. Interestingly, loss of function of MBNL1, an RNA-binding protein whose function is defective in DM1 patients, resulted in alteration of mTOR signaling, whereas gain-of-function experiments rescued the phenotype. Collectively, these results provide a mechanism by which DM1 mutation might affect a major signaling pathway and highlight the pertinence of using pluripotent stem cells to study neuronal defects.
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A potentially neuroprotective role for erythropoietin with paclitaxel treatment in ovarian cancer patients: a prospective phase II GINECO trial.
Support Care Cancer
PUBLISHED: 02-04-2013
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A prospective phase II multicenter study was performed in two steps in paclitaxel-treated ovarian cancer patients in France. A French version of the four-item Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire was validated. This was then used to evaluate neurotoxicity in relation to erythropoietin treatment.
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Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir.
J. Clin. Invest.
PUBLISHED: 01-14-2013
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Background. The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity involves ROS production, we investigated the efficacy of mangafodipir, a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer. Methods. The effects of mangafodipir were examined in mice following treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23 cancer patients with grade ?2 oxaliplatin-induced neuropathy in a phase II study, with 22 patients receiving i.v. mangafodipir following oxaliplatin. Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir. Results. Mangafodipir prevented motor and sensory dysfunction and demyelinating lesion formation. In mice, serum AOPPs decreased after 4 weeks of mangafodipir treatment. In 77% of patients treated with oxaliplatin and mangafodipir, neuropathy improved or stabilized after 4 cycles. After 8 cycles, neurotoxicity was downgraded to grade ?2 in 6 of 7 patients. Prior to enrollment, patients received an average of 880 ± 239 mg/m2 oxaliplatin. Patients treated with mangafodipir tolerated an additional dose of 458 ± 207 mg/m2 oxaliplatin despite preexisting neuropathy. Mangafodipir responders managed a cumulative dose of 1,426 ± 204 mg/m2 oxaliplatin. Serum AOPPs were lower in responders compared with those in nonresponders. Conclusion. Our study suggests that mangafodipir can prevent and/or relieve oxaliplatin-induced neuropathy in cancer patients. Trial registration. Clinicaltrials.gov NCT00727922. Funding. Université Paris Descartes, Ministère de la Recherche et de lEnseignement Supérieur, and Assistance Publique-Hôpitaux de Paris.
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A clinical experience of single agent bevacizumab in relapsing ovarian cancer.
Gynecol. Oncol.
PUBLISHED: 01-08-2013
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The objective of this study is to report the efficacy and tolerance of single agent bevacizumab (BEVA) in relapsing ovarian cancer patients treated in a single institution outside a clinical trial.
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A GINECO randomized phase II trial of two capecitabine and weekly paclitaxel schedules in metastatic breast cancer.
Breast Cancer Res. Treat.
PUBLISHED: 09-05-2011
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To determine whether capecitabine schedule adaptation improves the tolerability of capecitabine-paclitaxel combination therapy for metastatic breast cancer (MBC), patients with anthracycline-pretreated HER2-negative MBC were randomized to either arm A (21-day cycles: capecitabine 1,000 mg/m(2) twice daily, days 1-14; paclitaxel 60 mg/m(2), days 1, 8, and 15) or arm B (28-day cycles: capecitabine 1,000 mg/m(2) twice daily, days 1-5, 8-12, and 15-19; paclitaxel 80 mg/m(2), days 1, 8, and 15). The primary endpoint was the incidence of dose reductions or delays >1 week for grade 3/4 toxicity. Secondary endpoints were efficacy and safety. All 130 randomized patients were evaluable for safety. Dose reduction or delay for grade 3/4 toxicity occurred in 39% of patients in arm A and 34% in arm B during cycles 1-6. In arm A, there were significantly more toxicity-related dose reductions (cycles 1-6: 82 vs. 67%, respectively; P = 0.05) and discontinuations (29 vs. 8%, respectively). Grade 3 diarrhea occurred in 12 and 0%, respectively, and grade 3 hand-foot syndrome in 12 versus 9%, respectively (grade 4 not applicable). There were no detectable differences in efficacy. Weekday capecitabine dosing with weekly paclitaxel may improve tolerability without a detrimental effect on efficacy, and merits further evaluation in patients suited to combination chemotherapy.
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An observational study of bevacizumab-induced hypertension as a clinical biomarker of antitumor activity.
Oncologist
PUBLISHED: 08-01-2011
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Hypertension is a common toxicity of bevacizumab, but the frequency of assessment of blood pressure and standardized grading remain to be defined. This study aimed to describe the incidence of bevacizumab-induced hypertension and factors associated with its development, then to retrospectively assess its relation with activity.
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[Use of antioxidant and other complementary medicine by patients treated by antitumor chemotherapy: a prospective study].
Bull Cancer
PUBLISHED: 06-04-2011
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Use of complementary and alternative medicine (CAM) has been reported to be more and more frequent among cancer patients in USA. The aim of this study was to analyze among French cancer patients the prevalence of CAM use, focusing on antioxidants (AO) that could interfere with antitumor agents. Seventy-nine patients, treated by antitumor chemotherapy in oncology day care unit, participated to an interview (medium age ?= ?60 years old). CAM use was reported by 42% of patients: mostly AO (24%) (selenium, green tea and vitamins ACE, more specifically), but also relaxation, acupuncture, hypnosis (19%) and homeopathy (15%). Among patients using CAM, 66% of them indicated that their physicians were not aware of this use and 47% of them thought that CAM use was safe. Nevertheless, for seven patients who have taken AO, previous in vitro and preclinical studies suggested interactions with antitumor chemotherapy. Therefore, CAM use and, more specifically, AO use is common among cancer patients treated by antitumor chemotherapy in France. Nevertheless, AO could generate interactions with conventional treatment. Clinical studies are warranted to evaluate these interactions, and adequate communication with patients is needed.
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miR-203 modulates epithelial differentiation of human embryonic stem cells towards epidermal stratification.
Dev. Biol.
PUBLISHED: 05-20-2011
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The molecular mechanisms controlling the differentiation of human basal keratinocyte stem cells towards the epidermis are well characterized, whereas the earliest process leading to the specification of embryonic stem cells into keratinocytes is still not well understood. MicroRNAs are regulators of many cellular events, but evidence for microRNA acting on the differentiation of human embryonic stem cells into a specific lineage has been elusive. By using our recent protocol for obtaining functional keratinocytes from hESC, we attempted to analyze the role of microRNAs in the early stages of epidermal differentiation. Thus, we identified a set of 5 microRNAs, namely miR-200a, miR-200b, miR-203, miR-205 and miR-429, that are specifically overexpressed during the early stages of the differentiation process. Interestingly, our functional analyses revealed an instrumental role of miR-203, which had been previously shown to play a key role during the formation of the pluristratified epidermis by basal keratinocyte stem cells, in the early keratinocyte commitment. These results highlight the determinant and unique role of miR-203 during the entire process of epidermal development by extending its spectrum of action from the early commitment of embryonic stem cells to ultimate differentiation of the organ.
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Bystander effect of vinorelbine alters antitumor immune response.
Int. J. Cancer
PUBLISHED: 04-01-2011
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The bystander effect (BE) is the ability of malignant cells affected by an anticancer agent to induce damage in neighboring cancer cells. In this study, we showed that it could also affect immune cells surrounding the tumor and interfere with the antitumor immune response. We observed that the exposure of human lung cancer cells A549 to vinorelbine induced a BE on neighboring human peripheral blood mononuclear cells (PBMCs) in vitro and on mice splenocytes in vivo. In vitro, the number of PBMCs killed because of their coculture with vinorelbine-pretreated A549 cells was 33% higher than those killed by A549 control cells (p = 0.003). In addition, we showed that when vinorelbine-pretreated A549 cells were injected into immunocompetent mice, splenocyte proliferation ex vivo toward tumor cells decreased by 27% compared with that seen in mice injected with untreated A549 cells (p = 0.03). Finally, in vivo experiment in A549 tumor bearing nude mice showed that adoptive transfer of A549 immune splenocytes was not able to delay tumor growth when vinorelbine-pretreated A549 cells were used for immunization. Inhibition of the BE by the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester, and the superoxide dismutase mimic, mangafodipir, suggested that it was mediated by oxidative and nitrosative stress. In conclusion, exposure of cancer cells to vinorelbine alters the antitumor immune response through a BE mediated by cellular oxidative and nitrosative stress. Our results offer new prospects for using oxidative stress modulators to restore the antitumor immune response in patients treated with anticancer agents.
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CXCL12 expression by healthy and malignant ovarian epithelial cells.
BMC Cancer
PUBLISHED: 03-16-2011
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CXCL12 has been widely reported to play a biologically relevant role in tumor growth and spread. In epithelial ovarian cancer (EOC), CXCL12 enhances tumor angiogenesis and contributes to the immunosuppressive network. However, its prognostic significance remains unclear. We thus compared CXCL12 status in healthy and malignant ovaries, to assess its prognostic value.
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Safety of bevacizumab 7.5 mg/kg infusion over 10 minutes in NSCLC patients.
Invest New Drugs
PUBLISHED: 02-09-2011
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Bevacizumab is a humanized IgG1 monoclonal antibody against VEGF. Because infusion-related hypersensitivity reactions (HSRs) are a concern with monoclonal antibodies, initial phase 1 trials used a 90-, 60-, then 30-min initial infusion sequence. We evaluated the impact of a shortened bevacizumab infusion (10 min) on toxicity in nonsmall cell lung cancer (NSCLC) patients.
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Global transcriptional profiling of neural and mesenchymal progenitors derived from human embryonic stem cells reveals alternative developmental signaling pathways.
Stem Cells Dev.
PUBLISHED: 02-08-2011
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Human embryonic stem cells can be differentiated along different lineages, providing the possibility of a precise analysis of genes profiles associated with specific commitments. Subtractive gene expression profiling between differentiated and undifferentiated cells provides lists of potential actors in this commitment. This combines, however, genes that are specifically associated with development and others that are over expressed because of nonlineage-specific differentiation systems. As a way to establish gene profiles associated with the neural and/or to the mesodermal commitments of human embryonic stem cells more precisely, we have carried out a 2-step analysis. We first performed a subtractive analysis of gene profiles of each of these lineages as compared to the undifferentiated stage. Then, we extended the analysis by comparing the 2 sets of results with each other. This strategy has allowed us to eliminate large numbers of genes that were over expressed in both sets of results and to uniquely associate different gene networks with either the neural or the mesodermal commitments.
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Stimulation of angiogenesis resulting from cooperation between macrophages and MDA-MB-231 breast cancer cells: proposed molecular mechanism and effect of tetrathiomolybdate.
BMC Cancer
PUBLISHED: 07-17-2010
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Infiltration by macrophages (Mphi) indicates a poor prognosis in breast cancers, in particular by inducing angiogenesis. Our study aimed 1) to investigate the mechanism by which cooperation between Mphi and aggressive breast cancer cells (MDA-MB-231) induces angiogenesis; 2) to examine the effect of tetrathiomolybdate (TM) on this angiogenic activity.
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Hyper-alkalinization without hyper-hydration for the prevention of high-dose methotrexate acute nephrotoxicity in patients with osteosarcoma.
Cancer Chemother. Pharmacol.
PUBLISHED: 01-05-2010
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To evaluate the reliability and renal safety of an original schedule of high-dose methotrexate (HDMTX) administration with hyper-alkalinization, and without hyper-hydration.
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[Role of antioxidant complements and supplements in oncology in addition to an equilibrate regimen: a systematic review].
Bull Cancer
PUBLISHED: 06-05-2009
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Eating fruits and vegetables reduces risk of cancer by about 30%, however the active anticarcinogenic components of food remain to be determined. The well known oncogenic potential of oxidative stress have led to the use of antioxidants, contain in high proportions in fruits and vegetables, as cancer prevention. Numerous observational and interventional studies allowed to observe conflicting results. For example, in two major trials (CARET and ABTC) the risk of lung cancer was increased rather than reduced by beta-carotene supplements in smokers. Meta-analyses analyzing studies about supplementation in primary or tertiary prevention showed no benefit on overall survival regardless of tumor type studied or anti-oxidant evaluated. Those assessing the effect of non medical antioxidants taken during the anticancer treatments (chemotherapy or radiotherapy) indicate that if the objective of reducing side effects can sometimes be achieved, the risk of tumor progression and increasing mortality must not be disregarded. Because of the absence of formal effectiveness proof and potential risk of mortality, prophylactic supplementation with antioxidants can not be recommended. Varied and balanced diet of fruits and vegetables remains the best nutritional attitude to prevent the risk of cancer and should be promoted at all levels.
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Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?
Nat Rev Drug Discov
PUBLISHED: 05-29-2009
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Increased generation of reactive oxygen species (ROS) and an altered redox status have long been observed in cancer cells, and recent studies suggest that this biochemical property of cancer cells can be exploited for therapeutic benefits. Cancer cells in advanced stage tumours frequently exhibit multiple genetic alterations and high oxidative stress, suggesting that it might be possible to preferentially eliminate these cells by pharmacological ROS insults. However, the upregulation of antioxidant capacity in adaptation to intrinsic oxidative stress in cancer cells can confer drug resistance. Abrogation of such drug-resistant mechanisms by redox modulation could have significant therapeutic implications. We argue that modulating the unique redox regulatory mechanisms of cancer cells might be an effective strategy to eliminate these cells.
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Ambulatory administration of 5-day infusion ifosfamide+mesna: a pilot study in sarcoma patients.
Cancer Chemother. Pharmacol.
PUBLISHED: 05-09-2009
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Ifosfamide is a cornerstone of chemotherapy in bone and soft-tissue sarcoma. Results of pharmacokinetic studies indicate that the optimal schedule of ifosfamide should be repeated doses over several days. With the development of 5-day infusion devices, we developed and evaluated a 5-day infusion regimen of ifosfamide in sarcoma patients in the outpatient setting.
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Vinorelbine and oxaliplatin in stage IV nonsmall cell lung cancer patients unfit for cisplatin: a single-center experience.
Anticancer Drugs
PUBLISHED: 02-12-2009
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Many patients with stage IV nonsmall cell lung cancer (NSCLC) are unfit for cisplatin-based chemotherapy because of poor performance status, impaired renal function or severe comorbidity. We documented the feasibility of a combination of weekly vinorelbine and biweekly oxaliplatin in a population of stage IV NSCLC patients unable to receive cisplatin. Fifty-five chemo-naive patients (40 males, median age 60 years, range 43-84) were treated on an outpatient basis, and received every 2 weeks: vinorelbine 25 mg/m intravenously on day 1 and 60 mg/m orally on day 8, and oxaliplatin 85 mg/m intravenously on day 1. Patients were considered unfit for cisplatin because of performance status > or =2 (30 patients), impaired renal function (17 patients) or severe comorbidities (eight patients). Twenty-two patients (40%) had two or more metastatic sites, and 14 (25%) had central nervous system metastases. A total of 288 cycles were given (median per patient: 4, range 1-11). The planned dose intensity of vinorelbine was administered in 65% of patients. One complete and 13 partial responses were observed, providing an objective response rate of 26% (95% confidence interval: 14.4-37.6). The median progression-free survival and overall survival were 3.5 months and 9.5 months, respectively. The 1-year survival rate was 24% (95% confidence interval: 12.7-35.3). The main grade 3/4 toxicities were: neutropenia (15 patients, 27%), anaemia (12 patients, 22%) and peripheral neuropathy (eight patients, 15%). Three patients (5.5%) experienced febrile neutropenia. In a nonselected NSCLC patient population, the vinorelbine-oxaliplatin doublet had clinical activity in the same range as cisplatin-based combinations. This doublet allows combining a platinum derivative with a sustained dose intensity of vinorelbine in unfit patients.
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Predicting everolimus treatment efficacy in patients with advanced endometrial carcinoma: a GINECO group study.
Target Oncol
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This study aimed to determine whether the expression of various tumor biomarkers of the mTOR pathway predicts tumor response to everolimus in metastatic recurrent endometrial cancer. Tumor blocks from 44 patients of a phase II clinical trial receiving everolimus until progression or toxicity were collected and evaluated at 3 and 6 months for response. Thirty-six blocks were available for analysis of ER, PR, HER2, LKB1, PI3K, PTEN, pAKT, 4E-BP1, p4E-BP1, and S6RP expression by immunohistochemistry, PTEN deletion by FISH, and mutational status of K-RAS, PIK3CA, PTEN, and AKT1 genes. Twelve of 34 evaluable patients had partial response or stable disease (PR, SD) and 22 had progressive disease (PD). Immunohistochemistry showed that no protein expression could predict response to everolimus. Neither could loss of PTEN expression or PTEN deletion or PTEN mutation predict patient outcome. Thirty-one samples were assessable for K-RAS mutations (ten for PR+SD and 21 for PD). There are only four patients with K-RAS mutations and none of them responded to treatment. Median progression-free survival (PFS) and overall survival (OS) were longer in patients without K-RAS mutations (PFS 3.12?±?1.7 months versus 1.05?±?0.4 months, p?
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Cost effectiveness of integrated medicine in patients with cancer receiving anticancer chemotherapy.
J Oncol Pract
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Ambulatory chemotherapy is patient friendly but may result in toxicity-induced unscheduled hospitalizations (TIUHs). This emerging issue may increase health care costs. We studied the cost effectiveness of a hospital-home monitoring program based on systematic iterative telephone calls after chemotherapy.
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Arsenic trioxide exerts antitumor activity through regulatory T cell depletion mediated by oxidative stress in a murine model of colon cancer.
J. Immunol.
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Immunotherapy is a promising antitumor strategy that can successfully be combined with current anticancer treatment. In this study, arsenic trioxide (As(2)O(3)) was shown to increase the antitumor immune response in CT26 colon tumor-bearing mice through the modulation of regulatory T cell (T(reg)) numbers. As(2)O(3) induced T(reg)-selective depletion in vitro. In vivo, tumor-bearing mice injected with 1 mg/kg As(2)O(3) showed a significant decrease in the T(reg)/CD4 cell ratio and in absolute T(reg) count versus controls. As(2)O(3) exerted antitumor effects only in immunocompetent mice and enhanced adoptive immunotherapy effects. Inhibition of As(2)O(3)-induced T(reg) depletion by the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester and the superoxide dismutase mimic manganese [III] tetrakis-(5, 10, 15, 20)-benzoic acid porphyrin suggested that it was mediated by oxidative and nitrosative stress. The differential effect of As(2)O(3) on T(reg) versus other CD4 cells may be related to differences in the cells redox status, as indicated by significant differences in 27dichlorodihydrofluorescein diacetate and 4,5-diaminofluorescein diacetate fluorescence levels. In conclusion, these results show for the first time, to our knowledge, that low doses As(2)O(3) can delay solid tumor growth by depleting T(regs) through oxidative and nitrosative bursts, and suggest that As(2)O(3) could be used to enhance the antitumor activity of adoptive immunotherapy strategies in human cancer.
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Sorafenib-induced hepatocellular carcinoma cell death depends on reactive oxygen species production in vitro and in vivo.
Mol. Cancer Ther.
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Sorafenib is presently the only effective therapy in advanced hepatocellular carcinoma (HCC). Because most anticancer drugs act, at least in part, through the generation of reactive oxygen species, we investigated whether sorafenib can induce an oxidative stress. The effects of sorafenib on intracellular ROS production and cell death were assessed in vitro in human (HepG2) and murine (Hepa 1.6) HCC cell lines and human endothelial cells (HUVEC) as controls. In addition, 26 sera from HCC patients treated by sorafenib were analyzed for serum levels of advanced oxidation protein products (AOPP). Sorafenib significantly and dose-dependently enhanced in vitro ROS production by HCC cells. The SOD mimic MnTBAP decreased sorafenib-induced lysis of HepG2 cells by 20% and of Hepa 1.6 cells by 75% compared with HCC cells treated with 5 mg/L sorafenib alone. MnTBAP significantly enhanced by 25% tumor growth in mice treated by sorafenib. On the other hand, serum levels of AOPP were higher in HCC patients treated by sorafenib than in sera collected before treatment (P < 0.001). An increase in serum AOPP concentration ?0.2 ?mol/L chloramine T equivalent after 15 days of treatment is a predictive factor for sorafenib response with higher progression free survival (P < 0.05) and overall survival rates (P < 0.05). As a conclusion, sorafenib dose-dependently induces the generation of ROS in tumor cells in vitro and in vivo. The sera of Sorafenib-treated HCC patients contain increased AOPP levels that are correlated with the clinical effectiveness of sorafenib and can be used as a marker of effectiveness of the drug. .
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Pemetrexed, oxaliplatin and bevacizumab as first-line treatment in patients with stage IV non-small cell lung cancer.
Lung Cancer
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Oxaliplatin has less haematological toxicity than cisplatin and carboplatin. The combination of pemetrexed, oxaliplatin and bevacizumab appeared well tolerated and active as second- or third-line treatment in a previous phase II study. Its role as first-line therapy remains to define.
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Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells.
J. Clin. Invest.
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Human pluripotent stem cells offer a limitless source of cells for regenerative medicine. Neural derivatives of human embryonic stem cells (hESCs) are currently being used for cell therapy in 3 clinical trials. However, hESCs are prone to genomic instability, which could limit their clinical utility. Here, we report that neural differentiation of hESCs systematically produced a neural stem cell population that could be propagated for more than 50 passages without entering senescence; this was true for all 6 hESC lines tested. The apparent spontaneous loss of evolution toward normal senescence of somatic cells was associated with a jumping translocation of chromosome 1q. This chromosomal defect has previously been associated with hematologic malignancies and pediatric brain tumors with poor clinical outcome. Neural stem cells carrying the 1q defect implanted into the brains of rats failed to integrate and expand, whereas normal cells engrafted. Our results call for additional quality controls to be implemented to ensure genomic integrity not only of undifferentiated pluripotent stem cells, but also of hESC derivatives that form cell therapy end products, particularly neural lines.
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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.

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

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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.