Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells

Kamada, Masayuki; So, Alan; Muramaki, Mototsugu; Rocchi, Palma; Beraldi, Eliana; Gleave, Martin

doi:10.1158/1535-7163.mct-06-0417

Cited by 174 publications

(148 citation statements)

References 39 publications

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“…Several mechanisms account for the cytoprotective effect of Hsp27, including: (1) chaperone inhibitor of protein misfolding, (2) inhibition of key effectors of the apoptotic machinery at the pre-and post-mitochondrial level (Joza et al, 2001;Garrido et al, 2003;Rocchi et al, 2005Rocchi et al, , 2006 and (3) proteasome-mediated degradation of proteins under stress conditions (Garrido et al, 2006). Targeting Hsp27 by the second-generation ASO, OGX-427, inhibited Hsp27 expression and enhanced drug sensitivity in several xenograft models (Rocchi et al, 2004b(Rocchi et al, , 2005Kamada et al, 2007). A phase I/II clinical trial using OGX-427 in patients with prostate and other cancers is now underway in the United States and Canada (Hotte et al, 2009; http://www.oncogenex.ca/).…”

Section: Discussionmentioning

confidence: 99%

Heat shock protein 27 confers resistance to androgen ablation and chemotherapy in prostate cancer cells through eIF4E

et al. 2010

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Section: Discussionmentioning

confidence: 99%

Heat shock protein 27 confers resistance to androgen ablation and chemotherapy in prostate cancer cells through eIF4E

et al. 2010

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“…43,44 HSPs are highly conserved stress proteins induced by a variety of insults, such as hyperthermia and oxidative stress, 45,46 and their activation allows cells to survive and increases the tumorigenic potential of cancer cells. 47 In our series, HSP27 had great variability in staining intensity and distribution, and no significant differences were found between locally relapsed, metastatic, and disease-free GCTs.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Biomarkers for Giant Cell Tumor of Bone Using Comparative Proteomics Analysis

Conti

Rodriguez

Chiechi

et al. 2011

The American Journal of Pathology

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Giant cell tumor of bone can be locally aggressive and occasionally can metastasize in the lungs. To identify new markers predictive of aggressive behavior, we analyzed five patients who developed lung metastasis and five who remained disease free for a minimum of 5 years. Using two-dimensional electrophoresis, we detected 28 differentially expressed spots. Fourteen spots were identified using mass spectrometry, including seven up-regulated and seven down-regulated in metastatic samples and classified according to functional categories. We then selected five proteins involved in cell cycle or apoptosis. Thioredoxin peroxidase, allograft inflammatory factor 1, and ubiquitin E2N had more than threefold up-regulation; glutathione peroxidase 1 had 1.9-fold up-regulation; and heat shock protein 27 showed down-regulation in metastatic samples with a very low P value. After validation and analysis of protein levels, evaluation of clinical impact was assessed in a much wider cohort of primary archival specimens. Immunodetection showed a higher frequency of thioredoxin peroxidase, allograft inflammatory factor 1, ubiquitin E2N, and glutathione peroxidase 1 overexpression in primary tumors that developed into lung metastases or that locally relapsed than in the disease-free group, with variable stain intensity and distribution. KaplanMeier analysis showed that high expression of glutathi- Giant cell tumor (GCT) is a benign bone tumor with fairly high local aggressiveness, and development of lung metastases is rare, occurring in 2% to 5% of cases.1 Histologically, the tumor pattern is formed by a network of spindle-shaped mononuclear stroma cells, round mononuclear histiocytic cells, and multinuclear giant cells similar to osteoclasts.2 Cellular components interact with various factors playing a role in osteoclast function regulation. In fact, precursors of osteoclasts express receptor activator of NF-B that in the presence of macrophage colonystimulating factor and its ligand, receptor activator of NF-B ligand, mediates osteoclast formation by increasing the expression of enzymes that dissolve organic and inorganic components of bone.3,4 At the same time, the endogenous osteoprotegerin counteracts these effects by competing for receptor activator of NF-B ligand and neutralizing it. These interactions may provide information to help develop new approaches to biological therapy of this tumor. Drugs that target the osteolytic process lower recurrence rates associated with morbidity and mortality and are considered useful for new clinical treatments. 5,6

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“…HSPB1 plays crucial roles in carcinogenesis and progression through inhibition of cell apoptosis and senescence, two essential traits of cancer cells (48 -50). Various human cancers have been reported to exhibit overexpression of HSPB1, and the tumorigenic potentials of HSPB1 have been demonstrated in both experimental animal models and cell biologic studies (51)(52)(53). HSPB1 has been considered as an independent prognosis marker for cancers because its overexpression was involved in chemoradiotherapeutic resistance of tumor cells (54).…”

Section: Knockdown Of Gstp1 Increased the Susceptibility Of Human Bromentioning

confidence: 99%

Identification of Candidate Biomarkers for Early Detection of Human Lung Squamous Cell Cancer by Quantitative Proteomics

Zeng

Zhang

Deng

et al. 2012

Molecular & Cellular Proteomics

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To discover novel biomarkers for early detection of human lung squamous cell cancer (LSCC) and explore possible mechanisms of LSCC carcinogenesis, iTRAQ-tagging combined with two dimensional liquid chromatography tandem MS analysis was used to identify differentially expressed proteins in human bronchial epithelial carcinogenic process using laser capture microdissection-purified normal bronchial epithelium (NBE), squamous metaplasia (SM), atypical hyperplasia (AH), carcinoma in situ (CIS) and invasive LSCC. As a result, 102 differentially expressed proteins were identified, and three differential proteins (GSTP1, HSPB1 and CKB) showing progressively expressional changes in the carcinogenic process were selectively validated by Western blotting. Immunohistochemistry was performed to detect the expression of the three proteins in an independent set of paraffinembedded archival specimens including various stage tissues of bronchial epithelial carcinogenesis, and their ability for early detection of LSCC was evaluated by receiver operating characteristic analysis. The results showed that the combination of the three proteins could perfectly discriminate NBE from preneoplastic lesions (SM, AH and CIS) from invasive LSCC, achieving a sensitivity of 96% and a specificity of 92% in discriminating NBE from preneoplatic lesions, a sensitivity of 100% and a specificity of 98% in discriminating NBE from invasive LSCC, and a sensitivity of 92% and a specificity of 91% in discriminating preneoplatic lesions from invasive LSCC, respectively. Furthermore, we knocked down GSTP1 in immortalized human bronchial epithelial cell line 16HBE cells, and then measured their susceptibility to carcinogen benzo ( Lung cancer is the most frequently occurring malignancy with increasing incidence and is the leading cause of mortality in cancer-related deaths in China and worldwide (1, 2). Although great improvement has been made in diagnosis and treatment of lung cancer, the overall patients' survival is still very low and does not exceed 15% (3). The poor prognosis of this cancer is mainly explained by the fact that the diagnosis is generally made only at advanced stages because of the lack of reliable, early diagnostic biomarkers and the limited understanding of its carcinogenic mechanisms. Therefore, identification of biomarkers for early detection of lung cancer is mandatory, in turn leading to more effective treatment and reduction of mortality.Lung squamous cell carcinoma (LSCC) 1 originated from the bronchial epithelial cells is the most common histological type of lung cancer. It is known that carcinogenesis of LSCC is a multistage process and the result of multistep accumulation of genetic and epigenetic alterations (4). With exposure to environmental carcinogens, bronchial epithelial carcinogenesis often progresses in the following manner: hyperplasia, squamous metaplasia (SM), atypical hyperplasia (AH), cancer in situ (CIS) and invasive cancer (5). LSCC is the end-point of a whole range of morphological abnormalities that are dis-...

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Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells

Abstract: Heat shock protein 27 (Hsp27) is a cytoprotective chaperone that is phosphoactivated during cell stress that prevents aggregation and/or regulate activity and

Cited by 174 publications

References 39 publications

Heat shock protein 27 confers resistance to androgen ablation and chemotherapy in prostate cancer cells through eIF4E

Heat shock protein 27 confers resistance to androgen ablation and chemotherapy in prostate cancer cells through eIF4E

Identification of Potential Biomarkers for Giant Cell Tumor of Bone Using Comparative Proteomics Analysis

Identification of Candidate Biomarkers for Early Detection of Human Lung Squamous Cell Cancer by Quantitative Proteomics

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