Global gene expression analyses reveal changes in biological processes after hyperthermia in a rat glioma model

Borkamo, Erling Dahl; Dahl, Olav; Bruland, Ove; Fluge, Øystein

doi:10.1080/02656730802081997

Cited by 18 publications

(18 citation statements)

References 47 publications

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“…The gene expression levels are often stable for genes that are not affected by therapy, but those that are affected regularly change within hours. We have recently shown in rats that the initial gene expression burst is prominent and synchronized in the first hours after higher-temperature HT treatment compared with that achieved clinically, but only small changes in gene expression were detected after 1 day in the rodent model (5,6). This is in line with the data from the current study and may explain why no heat-shock proteins were differentially expressed in this study, including HSP90B1 and HSPH1.…”

Section: Discussionsupporting

confidence: 93%

“…Only 1 gene (MCM3) was detected by both the Japanese and American groups. None of the 53 genes were among the 1,213 genes differentially expressed within 3 h after HT treatment in an experimental glioma model in rats (5).…”

Section: Discussionmentioning

confidence: 99%

“…Altered gene expression signatures between biopsy specimens harvested before treatment and at mid treatment were also able to predict the response to celecoxib in addition to chemoradiation in LACC (4). We have analyzed global gene expression in a rat tumor model in vivo and in vitro and detected a wide range of differentially expressed genes during the first 3 h after HT treatment (5) but no significant differences from Day 1 to 21 (6). We present the results of the first exploratory study of gene expression changes after trimodality treatment with thermochemoradiation.…”

Section: Introductionmentioning

confidence: 98%

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cDNA Microarray Analysis of Serially Sampled Cervical Cancer Specimens From Patients Treated With Thermochemoradiotherapy

Borkamo

Schem

Fluge

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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cDNA Microarray Analysis of Serially Sampled Cervical Cancer Specimens From Patients Treated With Thermochemoradiotherapy

Borkamo

Schem

Fluge

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

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“…Recent DNA microarray and computational microarray analyzing technologies have provided a view of the expression (9,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). It is well known that cancer cells exposed to HT of more than 42.5˚C will undergo cell death, whereas exposure to MHT conditions, i.e., temperatures up to 42.5˚C, produces only slight or no cytotoxicity (26).…”

Section: Introductionmentioning

confidence: 99%

Gene networks related to the cell death elicited by hyperthermia in human oral squamous cell carcinoma HSC-3 cells

Tabuchi

Wada

Furusawa³

et al. 2011

Int J Mol Med

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Abstract. Local hyperthermia (HT) for various types of malignant tumors has shown promising antitumor effects. To confirm the detailed molecular mechanism underlying cell death induced by HT, gene expression patterns and gene networks in human oral squamous cell carcinoma (OSCC) cells were examined using a combination of DNA microarray and bioinformatics tools. OSCC HSC-3 cells were treated with HT at 44˚C for 90 min or mild hyperthermia (MHT) at 42˚C for 90 min, followed by culturing at 37˚C for 0-24 h. Treatment of cells with HT prevented cell proliferation (62%) and induced cell death (17%), whereas these alterations were not observed in cells treated with MHT. Microarray analysis revealed substantial differences with respect to gene expression patterns and biological function for the two different hyperthermic treatments. Moreover, we identified the temperature-specific gene networks D and H that were obtained from significantly up-regulated genes in the HT and MHT conditions, respectively, using Ingenuity pathway analysis tools. Gene network D, which contains 14 genes such as ATF3, DUSP1 and JUN, was associated with relevant biological functions including cell death and cellular movement. Gene network H, which contains 13 genes such as BAG3, DNAJB1 and HSPA1B, was associated with cellular function and maintenance and cellular assembly and organization. These findings provide a basis for understanding the detailed molecular mechanisms of cell death elicited by HT in human OSCC cells. IntroductionIn the treatment of oral squamous cell carcinoma (OSCC), treatment outcomes have improved in the past two decades due to progress in reconstructive techniques, stereotactic radiotherapy, new anticancer drugs such as taxanes, and combinations of these therapeutic modalities (1). Nonetheless, it is well known that patients with advanced tumors or tumor recurrence have a poor prognosis with a median survival period less than one year (2). Local hyperthermia (HT) for various malignant tumors including OSCC has been recognized as an effective and attractive tool with the advantages of relatively few side effects and slight damage to normal tissue. Combinations of HT with chemotherapy, radiotherapy or both have been clinically used for patients with cancer in various organs, and their antitumor effects have been verified by many clinical trials (3-7).In general, HT elicits a wide spectrum of stress responses such as induction of heat shock proteins (HSPs), protein aggregation, an imbalance of protein homeostasis, DNA and RNA damage, reactive oxygen species production, cell growth arrest and cell death in mammalian cells (8,9). In particular, HSPs, which are induced by heat, behave as molecular chaperones and exert strong cytoprotective effects that prevent cell death. The treatment of cells with HT induces numerous signal transduction pathways which contribute variously to cell death and survival (10-12). Although many biological processes are affected by HT, the overall responses to HT in mammalian cells remain unknown.Re...

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“…One way to achieve these objectives is through the use of microarrays to profile the gene expression of tumors associated with hyperthermia treatment. Although widespread genetic alterations, affecting many important physiologic pathways, have been identified in several studies (12–14), the intratumoral gene expression changes resulting from thermoradiotherapy and their relationship with tumor response are not well understood. Such definition of gene expression can also be analyzed with bioinformatics tools and other existing gene signatures representing specific biological pathways and processes.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Genomics and Functional Imaging from Canine Sarcomas Treated with Thermoradiotherapy Predicts Therapeutic Response and Identifies Combination Therapeutics

Chi

Thrall

Jiang

et al. 2011

Clinical Cancer Research

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Purpose: While hyperthermia is an effective adjuvant treatment to radiotherapy, we do not completely understand the nature of the response heterogeneity.Experimental Design: We performed gene expression analysis of 22 spontaneous canine sarcomas before and after the first hyperthermia treatment administered as an adjuvant to radiotherapy. In parallel, diffusion-weighted MRI (DWI) was done prior to the treatment course and at the end of therapy.Results: From the integrative analysis of gene expression and DWI, we identified significant correlation between tumor responses with genes involved in VEGF signaling, telomerase, DNA repair, and inflammation. The treatment-induced changes in gene expression identified 2 distinct tumor subtypes with significant differences in their gene expression and treatment response, as defined by changes in DWI. The 2 tumor subtypes could also be readily identified by pretreatment gene expression. The tumor subtypes, with stronger expression response and DWI increase, had higher levels of HSP70, POT1, and centrosomal proteins, and lower levels of CD31, vWF, and transferrin. Such differential gene expression between the 2 subtypes was used to interrogate connectivity map and identify linkages to an HSP90 inhibitor, geldanamycin. We further validated the ability of geldanamycin to enhance cell killing of human tumor cells with hyperthermia and radiotherapy in clonogenic assays.Conclusions: To our knowledge, this is one of the first successful attempts to link changes in gene expression and functional imaging to understand the response heterogeneity and identify compounds enhancing thermoradiotherapy. This study also demonstrates the value of canine tumors to provide information generalizable to human tumors.

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Global gene expression analyses reveal changes in biological processes after hyperthermia in a rat glioma model

Abstract: To our best knowledge, this is the first global microarray analysis of a malignant tumor treated with HT in vivo. We highlight biological processes affected by HT. RNA expression profiles also indicate a rapid suppression of the immune system within tumors by local HT.

Cited by 18 publications

References 47 publications

cDNA Microarray Analysis of Serially Sampled Cervical Cancer Specimens From Patients Treated With Thermochemoradiotherapy

cDNA Microarray Analysis of Serially Sampled Cervical Cancer Specimens From Patients Treated With Thermochemoradiotherapy

Gene networks related to the cell death elicited by hyperthermia in human oral squamous cell carcinoma HSC-3 cells

Comparison of Genomics and Functional Imaging from Canine Sarcomas Treated with Thermoradiotherapy Predicts Therapeutic Response and Identifies Combination Therapeutics

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