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Find video protocols related to scientific articles indexed in Pubmed.
Podoplanin-positive cancer-associated fibroblasts in the tumor microenvironment induce primary resistance to EGFR-TKIs in lung adenocarcinoma with EGFR mutation.
Clin. Cancer Res.
PUBLISHED: 11-13-2014
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Purpose: The biological characteristics of microenvironmental constituents, especially cancer-associated fibroblasts (CAFs), can be key regulators of the cellular sensitivity to molecular-targeted therapy. EGFR tyrosine kinase inhibitors (EGFR-TKIs) have marked therapeutic effects against non-small cell lung cancer (NSCLC) with EGFR mutations, but some patients have exhibited primary resistance to EGFR-TKIs. We recently reported that podoplanin (PDPN)-positive fibroblasts are associated with a tumor-promoting phenotype of CAFs in lung adenocarcinoma. The aim of this study was to evaluate whether the susceptibility of NSCLC to EGFR-TKIs could be affected by PDPN-expressing CAFs. Experimental Design: We evaluated the EGFR-TKI sensitivity of EGFR-mutant lung adenocarcinoma cell lines co-cultured with PDPN-expressing CAFs. We also examined the association between the expression of PDPN in CAFs in surgical specimens and EGFR-TKI response of postoperative recurrent patients with EGFR mutations (N = 106). Results: Lung adenocarcinoma cell lines became more resistant to EGFR-TKI when co-cultured with PDPN-expressing CAFs, compared with control CAFs in vitro. The knockdown of PDPN-expression on CAFs cancelled the resistance to EGFR-TKIs in cancer cells. Compared with control CAFs, the cancer cells that were co-cultured with PDPN-positive CAFs continued to exhibit significantly higher p-ERK levels after treatment with gefitinib. Furthermore, postoperative recurrent patients with PDPN-positive CAFs had a significantly lower overall response rate to EGFR-TKIs, compared with those with PDPN-negative CAFs (53% vs 83%, P < 0.01). Conclusions: PDPN-positive CAFs plays an important role in primary resistance to EGFR-TKIs and may be an ideal therapeutic target for use in combination therapy with EGFR-TKIs.
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Ezrin-expressing lung adenocarcinoma cells and podoplanin-positive fibroblasts form a malignant microenvironment.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 08-05-2014
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Cancer cells and cancer-associated fibroblasts (CAFs) together create the tumor microenvironment, which affects malignant behavior. Lung adenocarcinomas with CAFs expressing podoplanin (PDPN) are clinically aggressive, but the molecular mechanism underlying this phenomenon has not been established. So we identified the characteristic immunophenotype of lung adenocarcinoma cells coexisting with PDPN-expressing CAFs (PDPN-CAFs) and examined how it relates to an aggressive clinicopathological outcome.
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Work support for persons with mental disabilities in Japan.
Work
PUBLISHED: 03-13-2013
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The purpose of this paper is to review the methods and the activities of occupational therapists (OTs) in the field of work support for persons with mental disabilities in Japan.
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Morphophenotype of floating colonies derived from a single cancer cell has a critical impact on tumor-forming activity.
Pathol. Int.
PUBLISHED: 01-07-2013
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The anchorage-independent colony growth of cancer cells is reportedly correlated with the tumor-forming activity; however, the correlation between the morphophenotype of each colony and the tumor-forming activity has not been clarified. To assess this problem, we cultured single A549 cells (human lung adenocarcinoma cell line) in growth medium in individual wells (n = 426) for 14 days under anchorage-independent conditions and analyzed the resulting growth characteristics. The single A549 cells formed various sizes of floating colonies. The proportion of large colonies (>400 ?m) was 3.8% and this proportion increased dramatically with the exogenous addition of EGF (21.6%) or HGF (27.6%). Morphologically, the floating colonies could be divided into: (ii) Type A, spheroid colony; and (ii) Type B, dispersed villous colony. The Type B colonies expressed significantly higher levels of epithelial-mesenchymal transition (EMT)-related mRNAs (Snail 1, ZEB 1, and ZEB2) than the Type A colonies. Furthermore, the subcutaneous injection of a single cell-derived colony with a large size and a Type B morphology resulted in more efficient tumor formation. The present results indicated that the morphophenotypes of floating colonies derived from single cancer cells have a critical impact on tumor-forming activity.
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Fibroblasts associated with cancer cells keep enhanced migration activity after separation from cancer cells: a novel character of tumor educated fibroblasts.
Int. J. Oncol.
PUBLISHED: 07-03-2010
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It is now clear that the association between cancer cells and recruited fibroblasts (cancer-associated fibroblasts; CAFs) leads to alteration of the biological properties of both types of cells and creates a specific microenvironment. Here we report a novel biological property of CAFs and its cellular mechanism using in vivo and in vitro model. Cultured CAFs derived from human lung cancer tissue displayed significantly higher migration activity in response to PDGF-BB than that of fibroblasts from corresponding non-cancerous tissue (NCAFs). Moreover, KM104GFP (GFP-labeled human fibroblast cell line) co-cultured with human cancer cell line Capan-1 showed significantly higher migration activity than KM104GFP alone. No such phenomenon occurred when KM104GFP and Capan-1 were cultured separately. Even after KM104GFP were sorted from co-cultured Capan-1, KM104GFP retained their enhanced migration activity until passage-5 of culture in the absence of cancer cells. Despite a similar level of phosphorylation of ERK1/2 after exposure to PDGF-BB, the inhibitory effect of MEK inhibitor was significantly higher on migration of KM104GFP that had been sorted from co-cultured Capan-1 than of KM104GFP alone. This higher dependence on ERK1/2 signaling for cell migration was also seen in CAFs obtained from cancer tissue. The results of this study indicate that by association with cancer cells, CAFs can acquire enhanced migration activity which could be kept after separation from cancer cells and suggest the possibility that higher dependence on ERK1/2 signaling for enhanced migration activity would be one of the biological properties of CAFs.
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[Irradiation for invasive malignant thymoma led a remission of refractory minimal change nephrotic syndrome: a case report].
Nihon Jinzo Gakkai Shi
PUBLISHED: 06-22-2010
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A 46-year-old man was diagnosed as malignant thymoma, and was treated with chemotherapy and radiotherapy in 2003. On June 2004, he had edema of his legs and nephrotic syndrome (NS). As renal biopsy revealed a minor glomerular abnormality, he was diagnosed as minimal change nephrotic syndrome (MCNS). Intravenous steroid therapy of 500 mg/day for 3 days, following oral administration of 15 mg/day prednisolone and 75 mg cyclosporine twice a day was taken from July 2004. On July 2005, he went into remission of NS with 0.6 g/day proteinuria. On January 2008, NS relapsed with left pleural effusion. Chest CT and a biopsy specimen from left pleural mass lesion revealed the pleural invasion of malignant thymoma. Sixty Gray radiotherapy diminished the pleural metastatic lesion and also improved proteinuria from 6.6 g/day to 0.4 g/day. Though there have been a few case reports of MCNS concomitant with malignant thymoma, this is the first report that radiotherapy for metastatic malignant thymoma improved NS while diminishing the tumor.
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Aortic arch calcification detectable on chest X-ray is a strong independent predictor of cardiovascular events beyond traditional risk factors.
Atherosclerosis
PUBLISHED: 07-29-2009
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Arterial calcification makes the management of hemodynamics more difficult. Some reports have previously shown that simple assessment of aortic calcification using plain radiography is associated with cardiovascular (CV) events; however, these studies simply assessed whether aortic calcification was present or absent only, without considering its extent. Here, we evaluated validity of grading aortic arch calcification (AAC) to predict new CV events.
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Validity and usefulness of aortic arch calcification in chest X-ray.
J. Atheroscler. Thromb.
PUBLISHED: 06-25-2009
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Arterial calcification is associated with cardiovascular (CV) disease, to be leading to vessel wall stiffness and causing the management of hemodynamics in the elderly more difficult. Here, we compared the extent of calcification in the aortic arch by reviewing chest X-rays to that in the abdominal aorta as assessed by more detailed examinations. In addition, the validity of the grading and the relationship of this useful grading to clinical risk factors were evaluated.
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Tumor promoting effect of podoplanin-positive fibroblasts is mediated by enhanced RhoA activity.
Biochem. Biophys. Res. Commun.
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There is growing evidence that stromal fibroblasts can promote tumor progression via several mechanisms. We previously reported that podoplanin (PDPN) expressed on stromal fibroblasts is functionally protein responsible for the promotion of tumor formation in mouse subcutaneous tissue. The purpose of the present study was to reveal the molecular mechanism by which PDPN on stromal fibroblasts promotes tumor formation. The subcutaneous co-injection of the human lung adenocarcinoma cell line A549 and human fibroblasts (hFbs) overexpressing wild-type podoplanin (WT-PDPN) promoted subcutaneous tumor formation, compared with the co-injection of A549 and control hFbs (64% vs 21%). On the other hand, hFbs expressing PDPN mutant in which the cytoplasmic domain of PDPN was deleted (PDPN-Del.IC), resulted in a relatively lower level of tumor formation (33%). Since PDPN reportedly regulates RhoA activity through its cytoplasmic domain, we measured the activation state of RhoA in hFbs expressing WT-PDPN. RhoA activity was 2.7-fold higher in WT-PDPN expressing hFbs than in control hFbs. Furthermore, the subcutaneous co-injection of hFbs expressing constitutive active RhoA (G14VRhoA) and A549 cells enhanced tumor formation compared with the co-injection of the same cell line and control hFbs. These results indicate that enhanced RhoA activity in hFbs expressing PDPN may be one of the mechanisms resulting in the promotion of tumor formation, suggesting that biomechanical remodeling of the microenvironment by stromal fibroblasts may play important roles in tumor progression.
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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.