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Find video protocols related to scientific articles indexed in Pubmed.
Ionizing Radiation Sensitizes Breast Cancer Cells to Bcl-2 Inhibitor, ABT-737, through Regulating Mcl-1.
Radiat. Res.
PUBLISHED: 11-20-2014
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Breast-conserving surgery followed by radiation therapy has become the standard of care for early stage breast cancer. However, there are some patients that develop a local failure. We have previously shown that Bcl-2 overexpression was associated with an increased risk of local recurrence in patients with early stage breast cancer. The purpose of this study was to explore an approach to overcome radiation resistance by targeting pro-survival Bcl-2 family proteins in breast cancer cells. The breast cancer cell lines MCF-7, ZR-75-1 and MDA-MB231 were used in this study. siRNAs were employed to silence myeloid cell leukemia 1 (Mcl-1). A small molecule inhibitor of Bcl-2, ABT-737, was used to target anti-apoptotic Bcl-2 family proteins. Apoptosis was identified by FITC Annexin V, PI staining and Western blot analysis. The sensitivity to ionizing radiation and ABT-737 were measured by clonogenic assays. The effect of radiation and ABT-737 was also tested in a MCF-7 xenograft mouse model. Our data demonstrate that the combination of ABT-737 and radiation-induced apoptosis had an inhibitory effect on breast cancer cell proliferation. However, treatment with ABT-737 resulted in elevated Mcl-1 in breast cancer cell lines. Targeting Mcl-1 by siRNA sensitized MCF-7 cells to ABT-737. We revealed that radiation blunted Mcl-1 elevation induced by ABT-737, and that radiation downregulated Mcl-1 by promoting its degradation. Our results indicate that radiation and ABT-737 exert a synergistic effect on breast cancer cell lines through downregulating Mcl-1 and activating the bak-apoptotic pathway. These results support the combination of radiation and pro-survival Bcl-2 family inhibitor as a potential novel therapeutic strategy in the local-regional management of breast cancer.
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Autophagy inhibition by chloroquine sensitizes HT-29 colorectal cancer cells to concurrent chemoradiation.
World J Gastrointest Oncol
PUBLISHED: 01-11-2014
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To investigate whether the inhibition of autophagy by chloroquine (CQ) sensitizes rectal tumors to radiation therapy (RT) or concurrent chemoradiation (chemoRT).
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Is Ki-67 expression prognostic for local relapse in early-stage breast cancer patients treated with breast conservation therapy (BCT)?
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 03-15-2013
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Ki-67 is a human nuclear protein whose expression is strongly up-regulated in proliferating cells and can be used to determine the growth fraction in clonal cell populations. Although there are some data to suggest that Ki-67 overexpression may be prognostic for endpoints such as survival or postmastectomy recurrence, further elucidation of its prognostic significance is warranted. Specifically after breast conservation therapy (BCT) (defined in this setting as breast-conserving surgery and adjuvant radiation therapy), whether Ki-67 predicts for locoregional recurrence has not been investigated. The purpose of this study was to assess Ki-67 expression in a cohort of early-stage breast cancer patients to determine whether a significant independent association between Ki-67 and locoregional relapse exists.
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Riluzole enhances ionizing radiation-induced cytotoxicity in human melanoma cells that ectopically express metabotropic glutamate receptor 1 in vitro and in vivo.
Clin. Cancer Res.
PUBLISHED: 02-15-2011
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Brain metastases are a common preterminal event in patients with metastatic melanoma and require radiation therapy. Our group has previously shown that human GRM1 (hGRM1) expressing melanoma cells release excess extracellular glutamate and are growth inhibited by riluzole, an inhibitor of glutamate release. Riluzole-treated cells accumulate in G(2)/M phase of the cell cycle at 24 hours, and then undergo apoptotic cell death. We evaluated whether riluzole enhanced radiosensitivity in melanoma cells.
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Evaluation of single nucleotide polymorphisms (SNPs) in the p53 binding protein 1 (TP53BP1) gene in breast cancer patients treated with breast-conserving surgery and whole-breast irradiation (BCS + RT).
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-04-2010
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TP53BP1 is a key component of radiation-induced deoxyribonucleic acid damage repair. The purpose of this study was to evaluate the significance of a known common single nucleotide polymorphism in this gene (rs560191) in patients treated with breast-conserving surgery and whole-breast irradiation (BCS + RT).
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Mediator of DNA damage checkpoint protein 1 (MDC1) expression as a prognostic marker for nodal recurrence in early-stage breast cancer patients treated with breast-conserving surgery and radiation therapy.
Breast Cancer Res. Treat.
PUBLISHED: 02-03-2010
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The mediator of DNA damage checkpoint protein 1 (MDC1) regulates cell cycle checkpoints and recruits repair proteins to sites of double-stranded DNA damage using its BRCA1 carboxy-terminal (BRCT) domains. MDC1 under-expression has been associated with radiosensitivity in cells. The purpose of this study was to evaluate the clinico-pathologic and prognostic significance of MDC1 expression in a cohort of early-stage breast cancer patients treated with breast conservation therapy. Paraffin specimens from 489 women with early-stage breast cancer treated with breast conservation therapy were constructed into tissue microarrays. The arrays were stained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and MDC1. This was correlated with clinico-pathologic factors and outcomes. MDC1 expression was evaluable in 351 cases (72%). Decreased MDC1 expression was found to be correlated with nodal failure (P = 0.05), but not ipsilateral breast relapse-free survival (IBRFS), distant metastasis-free survival (DMFS), or overall survival (OS). Subset analysis in node-negative patients revealed that decreased MDC1 expression predicted for nodal failure (P < 0.01). Our study is the first to assess the clinico-pathologic and prognostic significance of MDC1 expression in patients with early-stage breast cancer treated with lumpectomy and radiotherapy. MDC1 under-expression predicted for nodal failure, but not for IBRFS, DM, or OS. The role of other proteins involved in the DNA damage repair pathway and their effects on MDC1 expression, as well as the level of MDC1 expression in patients with BRCA1 mutations warrant further investigation.
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Clinicopathologic significance of excision repair cross-complementation 1 expression in patients treated with breast-conserving surgery and radiation therapy.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-18-2009
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The excision repair cross-complementation 1 (ERCC1) enzyme plays a rate-limiting role in the nucleotide excision repair pathway and is associated with resistance to platinum-based chemotherapy in cancers of the head and neck and the lung. The purpose of this study was to evaluate the clinicopathologic and prognostic significance of ERCC1 expression in a cohort of early-stage breast cancer patients treated with breast conservation therapy.
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Low p53 binding protein 1 (53BP1) expression is associated with increased local recurrence in breast cancer patients treated with breast-conserving surgery and radiotherapy.
Int. J. Radiat. Oncol. Biol. Phys.
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To investigate whether the expression of p53 binding protein 1 (53BP1) has prognostic significance in a cohort of early-stage breast cancer patients treated with breast-conserving surgery and radiotherapy (BCS+RT).
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Disruption of GRM1-mediated signalling using riluzole results in DNA damage in melanoma cells.
Pigment Cell Melanoma Res
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Gain-of-function of the neuronal receptor, metabotropic glutamate receptor 1 (Grm1), was sufficient to induce melanocytic transformation in vitro and spontaneous melanoma development in vivo when ectopically expressed in melanocytes. The human form of this receptor, GRM1, has been shown to be ectopically expressed in a subset of human melanomas but not benign nevi or normal melanocytes, suggesting that misregulation of GRM1 is involved in the pathogenesis of certain human melanomas. Sustained stimulation of Grm1 by the ligand, glutamate, is required for the maintenance of transformed phenotypes in vitro and tumorigenicity in vivo. In this study we investigate the mechanism of an inhibitor of glutamate release, riluzole, on human melanoma cells that express metabotropic glutamate receptor 1 (GRM1). Various in vitro assays conducted show that inhibition of glutamate release in several human melanoma cell lines resulted in an increase of oxidative stress and DNA damage response markers. This article is protected by copyright. All rights reserved.
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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.