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Find video protocols related to scientific articles indexed in Pubmed.
OSU-T315: a novel targeted therapeutic that antagonizes AKT membrane localization and activation of chronic lymphocytic leukemia cells.
Blood
PUBLISHED: 10-09-2014
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Aberrant regulation of endogenous survival pathways plays a major role in progression of chronic lymphocytic leukemia (CLL). Signaling via conjugation of surface receptors within the tumor environmental niche activates survival and proliferation pathways in CLL. Of these, the PI3K/AKT pathway appears to be pivotal to support CLL pathogenesis, and pharmacologic inhibitors targeting this axis have shown clinical activity. Here we investigate OSU-T315, a compound that disrupts the Phosphoinositide 3-kinase (PI3K)/AKT pathway in a novel manner. Dose-dependent, selective cytotoxicity by OSU-T315 is noted in both CLL-derived cell lines and primary CLL cells relative to normal lymphocytes. In contrast to the highly successful BTK and PI3K inhibitors that inhibit BCR signaling pathway at proximal kinases, OSU-T315 directly abrogates AKT activation by preventing translocation of AKT into lipid rafts without altering the activation of receptor-associated kinases. Through this mechanism, the agent triggers caspase-dependent apoptosis in CLL by suppressing BCR, CD49d, CD40 and TLR9-mediated AKT activation in an ILK-independent manner. In vivo, OSU-T315 attains pharmacologically active drug levels and significantly prolongs survival in the TCL1 mouse model. Together, our findings indicate a novel mechanism of action of OSU-T315 with potential therapeutic application in CLL.
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CBB1003, a lysine-specific demethylase 1 inhibitor, suppresses colorectal cancer cells growth through down-regulation of leucine-rich repeat-containing G-protein-coupled receptor 5 expression.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 04-16-2014
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Lysine-specific demethylase 1 (LSD1) was highly expressed in several malignancies and had been implicated in pathological processes of cancer cells. However, the role of LSD1 in colorectal cancer (CRC) carcinogenesis, prognosis and treatment remains uncharacterized.
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Rectal cancer level significantly affects rates and patterns of distant metastases among rectal cancer patients post curative-intent surgery without neoadjuvant therapy.
World J Surg Oncol
PUBLISHED: 01-07-2014
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Rectal cancer patients have a higher incidence of pulmonary metastases than those with colon cancer. This study aimed to examine the effects of rectal cancer level on recurrence patterns in rectal cancer patients.
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Anorectal melanoma: review of 22 consecutive cases.
Hepatogastroenterology
PUBLISHED: 07-24-2013
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To evaluate outcome and prognostic factors of patients with anorectal melanoma.
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Concurrent chemoradiotherapy in the treatment of locally recurrent rectal cancer.
Hepatogastroenterology
PUBLISHED: 07-24-2013
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Long course concurrent chemoradiotherapy provides potential tumor downstaging. When local recurrent rectal cancer without distant metastases is diagnosed, a potentially curative resection can be performed. The aim of this study was to assess the outcome of concurrent chemoradiotherapy in treating isolated local recurrent rectal cancer.
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Immunohistochemical study of vascular endothelial growth factor (VEGF) and matrilysin (MMP-7) in T1 adenocarcinoma of the colon and rectum to predict lymph node metastases or distant metastases.
Hepatogastroenterology
PUBLISHED: 10-26-2011
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Predicting the lymph node metastatic or distant metastatic potential of T1 adenocarcinoma of the colon and rectum remains a major challenge. We investigated the role of the expressions of tumor matrilysin (MMP-7), VEGF-C and VEGF-A in predicting these metastatic potentials.
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Preoperative carcinoembryonic antigen elevation in colorectal cancer.
Hepatogastroenterology
PUBLISHED: 09-23-2011
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BACKGROUND /AIMS: The aim of this study was to calculate the prevalence of elevated carcinoembryonic antigen (CEA) among colorectal cancer (CRC) patients and to evaluate the prognostic value of preoperative serum CEA levels in them.
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The identification and analysis of phosphorylation sites on the Atg1 protein kinase.
Autophagy
PUBLISHED: 07-01-2011
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Autophagy is a conserved, degradative process that has been implicated in a number of human diseases and is a potential target for therapeutic intervention. It is therefore important that we develop a thorough understanding of the mechanisms regulating this trafficking pathway. The Atg1 protein kinase is a key element of this control as a number of signaling pathways target this enzyme and its associated protein partners. These studies have established that Atg1 activities are controlled, at least in part, by protein phosphorylation. To further this understanding, we used a combined mass spectrometry and molecular biology approach to identify and characterize additional sites of phosphorylation in the Saccharomyces cerevisiae Atg1. Fifteen candidate sites of phosphorylation were identified, including nine that had not been noted previously. Interestingly, our data suggest that the phosphorylation at one of these sites, Ser-34, is inhibitory for both Atg1 kinase activity and autophagy. This site is located within a glycine-rich loop that is highly conserved in protein kinases. Phosphorylation at this position in several cyclin-dependent kinases has also been shown to result in diminished enzymatic activity. In addition, these studies identified Ser-390 as the site of autophosphorylation responsible for the anomalous migration exhibited by Atg1 on SDS-polyacrylamide gels. Finally, a mutational analysis suggested that a number of the sites identified here are important for full autophagy activity in vivo. In all, these studies identified a number of potential sites of regulation within Atg1 and will serve as a framework for future work with this enzyme.
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An Atg13 protein-mediated self-association of the Atg1 protein kinase is important for the induction of autophagy.
J. Biol. Chem.
PUBLISHED: 06-28-2011
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Autophagy pathways in eukaryotic cells mediate the turnover of a diverse set of cytoplasmic components, including damaged organelles and abnormal protein aggregates. Autophagy-mediated degradation is highly regulated, and defects in these pathways have been linked to a number of human disorders. The Atg1 protein kinase appears to be a key site of this control and is targeted by multiple signaling pathways to ensure the appropriate autophagic response to changing environmental conditions. Despite the importance of this kinase, relatively little is known about the molecular details of Atg1 activation. In this study we show that Atg13, an evolutionarily conserved regulator of Atg1, promotes the formation of a specific Atg1 self-interaction in the budding yeast, Saccharomyces cerevisiae. The appearance of this Atg1-Atg1 complex is correlated with the induction of autophagy, and conditions that disrupt this complex result in diminished levels of both autophagy and Atg1 kinase activity. Moreover, the addition of a heterologous dimerization domain to Atg1 resulted in elevated kinase activity both in vivo and in vitro. The formation of this complex appears to be an important prerequisite for the subsequent autophosphorylation of Thr-226 in the Atg1 activation loop. Previous work indicates that this modification is necessary and perhaps sufficient for Atg1 kinase activity. Interestingly, this Atg1 self-association does not require Atg17, suggesting that this second conserved regulator might activate Atg1 in a manner mechanistically distinct from that of Atg13. In all, this work suggests a model whereby this self-association stimulates the autophosphorylation of Atg1 within its activation loop.
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Long-term survival benefits of adjuvant chemotherapy by decreasing incidence of tumor recurrence without delaying relapse in stage III colorectal cancer.
Int J Colorectal Dis
PUBLISHED: 04-11-2011
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To elucidate the survival benefits of adjuvant chemotherapy by decreasing incidence or by delaying time of tumor recurrence, we reported the long-term results of a nonrandomized prospective study comparing the adjuvant chemotherapy to no chemotherapy in stage III colorectal cancer.
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Effect of preoperative neutrophil-lymphocyte ratio on the surgical outcomes of stage II colon cancer patients who do not receive adjuvant chemotherapy.
Int J Colorectal Dis
PUBLISHED: 03-04-2011
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Selection of appropriate stage II colon cancer patients for adjuvant chemotherapy is critical for improving survival outcome. With the aim of identifying more high risk factors for stage II colon cancer, this study aimed to determine whether the neutrophil-lymphocyte ratio (NLR) is a predictor of surgical outcomes in patients with stage II colon cancer who do not receive adjuvant chemotherapy.
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Surgical resection of locally advanced primary transverse colon cancer--not a worse outcome in stage II tumor.
Int J Colorectal Dis
PUBLISHED: 01-16-2011
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In locally advanced primary transverse colon cancer, a tumor may cause perforation or invade adjacent organs. Extensive resection is the best choice of treatment, but such procedures must be weighed against the potential survival benefits. This study was performed to identify the clinicopathological features and treatment outcomes of such tumors.
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Low preoperative serum albumin in colon cancer: a risk factor for poor outcome.
Int J Colorectal Dis
PUBLISHED: 12-03-2010
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The number of colon cancer patients is increasing worldwide. Malnutrition and comorbidities are frequently associated with these patients. The relationships between the preoperative malnutrition and the outcomes of colon cancer patients are unclear; this study aimed to clarify these issues.
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Autophosphorylation within the Atg1 activation loop is required for both kinase activity and the induction of autophagy in Saccharomyces cerevisiae.
Genetics
PUBLISHED: 05-03-2010
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Autophagy is an evolutionarily conserved degradative pathway that has been implicated in a number of physiological events important for human health. This process was originally identified as a response to nutrient deprivation and is thought to serve in a recycling capacity during periods of nutritional stress. Autophagy activity appears to be highly regulated and multiple signaling pathways are known to target a complex of proteins that contains the Atg1 protein kinase. The data here extend these observations and identify a particular phosphorylation event on Atg1 as a potential control point within the autophagy pathway in Saccharomyces cerevisiae. This phosphorylation occurs at a threonine residue, T226, within the Atg1 activation loop that is conserved in all Atg1 orthologs. Replacing this threonine with a nonphosphorylatable residue resulted in a loss of Atg1 protein kinase activity and a failure to induce autophagy. This phosphorylation required the presence of a functional Atg1 kinase domain and two known regulators of Atg1 activity, Atg13 and Atg17. Interestingly, the levels of this modification were found to increase dramatically upon exposure to conditions that induce autophagy. In addition, T226 phosphorylation was associated with an autophosphorylated form of Atg1 that was found specifically in cells undergoing the autophagy process. In all, these data suggest that autophosphorylation within the Atg1 activation loop may represent a point of regulatory control for this degradative process.
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Clinical outcome of signet ring cell carcinoma and mucinous adenocarcinoma of the colon.
Chang Gung Med J
PUBLISHED: 02-27-2010
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The purpose of this study was to evaluate the clinicopathologic features and prognosis of signet ring cell carcinoma (SCC) and non-SCC mucinous adenocarcinoma (MC) and to compare them with those of nonmucinous adenocarcinoma (NMC) of the colon.
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The Tor and cAMP-dependent protein kinase signaling pathways coordinately control autophagy in Saccharomyces cerevisiae.
Autophagy
PUBLISHED: 02-06-2010
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Macroautophagy (hereafter autophagy) is a conserved membrane trafficking pathway responsible for the turnover of cytosolic protein and organelles during periods of nutrient deprivation. This pathway is also linked to a number of processes important for human health, including tumor suppression, innate immunity and the clearance of protein aggregates. As a result, there is tremendous interest in autophagy as a potential point of therapeutic intervention in a variety of pathological states. To achieve this goal, it is imperative that we develop a thorough understanding of the normal regulation of this process in eukaryotic cells. The Tor protein kinases clearly constitute a key element of this control as Tor activity inhibits this degradative process in all organisms examined, from yeast to man. Here, we discuss recent work indicating that the cAMP-dependent protein kinase (PKA) also plays a critical role in controlling autophagy in the budding yeast, Saccharomyces cerevisiae. A model describing how PKA activity might influence this degradative process, and how this control might be integrated with that of the Tor pathway, is presented.
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Lead time of carcinoembryonic antigen elevation in the postoperative follow-up of colorectal cancer did not affect the survival rate after recurrence.
Int J Colorectal Dis
PUBLISHED: 01-08-2010
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The role of carcinoembryonic antigen (CEA) in the early detection of recurrence during the postoperative follow-up of colorectal cancer remains unclear. We hypothesize that the tumor with longer lead time of CEA elevation to the definite recurrence may have a better prognosis because of its slower growth rate and closer observation.
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The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-21-2009
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Macroautophagy (or autophagy) is a conserved degradative pathway that has been implicated in a number of biological processes, including organismal aging, innate immunity, and the progression of human cancers. This pathway was initially identified as a cellular response to nutrient deprivation and is essential for cell survival during these periods of starvation. Autophagy is highly regulated and is under the control of a number of signaling pathways, including the Tor pathway, that coordinate cell growth with nutrient availability. These pathways appear to target a complex of proteins that contains the Atg1 protein kinase. The data here show that autophagy in Saccharomyces cerevisiae is also controlled by the cAMP-dependent protein kinase (PKA) pathway. Elevated levels of PKA activity inhibited autophagy and inactivation of the PKA pathway was sufficient to induce a robust autophagy response. We show that in addition to Atg1, PKA directly phosphorylates Atg13, a conserved regulator of Atg1 kinase activity. This phosphorylation regulates Atg13 localization to the preautophagosomal structure, the nucleation site from which autophagy pathway transport intermediates are formed. Atg13 is also phosphorylated in a Tor-dependent manner, but these modifications appear to occur at positions distinct from the PKA phosphorylation sites identified here. In all, our data indicate that the PKA and Tor pathways function independently to control autophagy in S. cerevisiae, and that the Atg1/Atg13 kinase complex is a key site of signal integration within this degradative pathway.
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Metastatic lymph node ratio is a more precise predictor of prognosis than number of lymph node metastases in stage III colon cancer.
Int J Colorectal Dis
PUBLISHED: 05-13-2009
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The objective of this study is to assess the value of metastatic lymph node ratio (LNR) in predicting disease-free survival (DFS) in patients with stage III adenocarcinoma of the colon.
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Effect of body mass index on the outcome of patients with rectal cancer receiving curative anterior resection: disparity between the upper and lower rectum.
Ann. Surg.
PUBLISHED: 04-24-2009
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The aim of this study was to investigate the effect of body mass index (BMI) on local recurrence of primary rectal cancer after open curative sphincter-saving resection.
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Serum p53 antibody as tumor marker for follow-up of colorectal cancer after curative resection.
Ann. Surg. Oncol.
PUBLISHED: 04-15-2009
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No large-scale studies have examined the use of serial measurements of serum p53 antibodies (s-p53Abs) combined with carcinoembryonic antigen (CEA) measurements during the follow-up of colorectal cancer (CRC) patients after curative resection.
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Increases of quadriceps inter-muscular cross-correlation and coherence during exhausting stepping exercise.
Sensors (Basel)
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The aim of this study was to examine the change of the intermuscular cross-correlation and coherence of the rectus femoris (RF), vastus medialis (VM) and vastus lateralis (VL) during exhausting stepping exercise. Eleven healthy adults repeated the stepping exercise up to their individual endurance limits (RPE score reached 20), and the cross-correlation and coherence were assessed by surface electromyography (EMG) recordings. The coefficient and time lag of cross-correlation and the coherence areas in the alpha (8-12 Hz), beta (15-30 Hz), gamma (30-60 Hz) and high-gamma (60-150 Hz) bands among the three muscle pairs (RF-VM, RF-VL and VM-VL) were calculated. As muscle fatigue, RF-VM and VM-VL showed increases of coefficients and the shortening of time lags. RF-VM and RF-VL showed increases of beta-band coherence in the ascent and descent phases, respectively. The increased intermuscular cross-correlation and beta-band coherence may be a compensatory strategy for maintaining the coordination of knee synergistic muscles during fatigue due to the fatigue-related disturbance of the corticospinal transmission. Therefore, the intermuscular cross-correlation and beta-band coherence may be a potential index for assessing muscle fatigue and monitoring the central control of motor function during dynamic fatiguing exercise.
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[Increasing patient family member satisfaction with information received from a post-anesthesia care unit].
Hu Li Za Zhi
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Families of patients in post-anesthesia care units (PACUs), often feel anxious because of a lack of information on patient condition and post-operative care. Based on interviews with families, we designed a family information needs questionnaire to measure family information needs, satisfaction with information received, satisfaction with post-operative care, and level of perceived anxiety. Results of a questionnaire survey taken in March 2011 revealed an average satisfaction-level score of 75.5%. Factors negatively affecting satisfaction included lack of orientation information on the PACU, unclear PACU navigation information, and general comprehension difficulties due to anxiety.
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Role of body mass index in colon cancer patients in Taiwan.
World J. Gastroenterol.
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To determine the effect of body mass index (BMI) on the characteristics and overall outcome of colon cancer in Taiwan.
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ER stress and autophagy: new discoveries in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol.
Blood
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Cyclin dependent kinase (CDK) inhibitors, such as flavopiridol, demonstrate significant single-agent activity in chronic lymphocytic leukemia (CLL), but the mechanism of action in these nonproliferating cells is unclear. Here we demonstrate that CLL cells undergo autophagy after treatment with therapeutic agents, including fludarabine, CAL-101, and flavopiridol as well as the endoplasmic reticulum (ER) stress-inducing agent thapsigargin. The addition of chloroquine or siRNA against autophagy components enhanced the cytotoxic effects of flavopiridol and thapsigargin, but not the other agents. Similar to thapsigargin, flavopiridol robustly induces a distinct pattern of ER stress in CLL cells that contributes to cell death through IRE1-mediated activation of ASK1 and possibly downstream caspases. Both autophagy and ER stress were documented in tumor cells from CLL patients receiving flavopiridol. Thus, CLL cells undergo autophagy after multiple stimuli, including therapeutic agents, but only with ER stress mediators and CDK inhibitors is autophagy a mechanism of resistance to cell death. These findings collectively demonstrate, for the first time, a novel mechanism of action (ER stress) and drug resistance (autophagy) for CDK inhibitors, such as flavopiridol in CLL, and provide avenues for new therapeutic combination approaches in this disease.
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Tetraspanin CD37 directly mediates transduction of survival and apoptotic signals.
Cancer Cell
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Tetraspanins are commonly believed to act only as "molecular facilitators," with no direct role in signal transduction. We herein demonstrate that upon ligation, CD37, a tetraspanin molecule expressed on mature normal and transformed B cells, becomes tyrosine phosphorylated, associates with proximal signaling molecules, and initiates a cascade of events leading to apoptosis. Moreover, we have identified two tyrosine residues with opposing regulatory functions: one lies in the N-terminal domain of CD37 in a predicted "ITIM-like" motif and mediates SHP1-dependent death, whereas the second lies in a predicted "ITAM motif" in the C-terminal domain of CD37 and counteracts death signals by mediating phosphatidylinositol 3-kinase-dependent survival.
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Risk factors for lymph node metastasis in pT1 and pT2 rectal cancer: a single-institute experience in 943 patients and literature review.
Ann. Surg. Oncol.
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Local excision has become an alternative for radical resection in rectal cancer for selected patients. The purpose of this study was to assess the clinicopathologic factors determining lymph node metastasis (LNM) in patients with T1-2 rectal cancer.
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Impact of chemotherapy-related prognostic factors on long-term survival in patients with stage III colorectal cancer after curative resection.
Int. J. Clin. Oncol.
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This retrospective study evaluated the prognostic factors of chemotherapy in stage III colorectal cancer after curative resection.
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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.