Gene expression profiles classifies the responsiveness of human osteosarcoma to doxorubicin, cisplatin and ifosfamide

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9534-9534
Author(s):  
S. Bruheim ◽  
Y. Xi ◽  
G. Nakajima ◽  
J. Ju ◽  
O. Fodstad

9534 Background: Despite the increased survival rates of osteosarcoma patients attributed to adjuvant chemotherapy, at least one third of the patients still succumb to their disease. Furthermore, ultra-aggressive combination chemotherapy is associated with considerable acute and long term toxicity. This is of particular concern in patients who may be cured by a simpler and less toxic regimens or do not have micrometastatic disease. Hence, further improvements in the management of osteosarcoma seemingly depend on diagnostic and prognostic tools that may allow for a more risk adapted and individualized treatment. Methods: We have used GE Uniset Human 20K microarrays to obtain gene expression profiles from a panel of ten unique human osteosarcoma xenografts. For each of the three drugs doxorubicin, cisplatin or ifosfamide the xenografts were grouped according to their response to chemotherapy, resistant, weakly sensitive or sensitive. For each individual drug, a one-way ANOVA test with a Benjamini and Hochberg multiple test correction allowing a false discovery rate of 5% (doxorubicin, cisplatin) or 2% (ifosfamide) was used to identify genes with significantly differential expression. In addition a 2-fold cut off was applied to exclude smaller but yet significant differences. Results: For doxorubicin and cisplatin, respectively 59 and 120 genes met these criteria. The expression levels of 25 genes overlapped between these two groups. For ifosfamide, 148 genes were selected, for 5 of them the expression overlapped with cisplatin sensitivity related genes. In the lists, genes involved in mediating and regulating apoptosis were abundant, such as regulators of TGF signaling, ubiquitin mediated protein degradation and members of the immediate early response protein family. Several genes which products interact with components of the cytoskeleton were also identified. Conclusion: We have used a unique strategy to screen for potential chemosensitivity markers by utilizing xenografts as training sets. No significant financial relationships to disclose.

2005 ◽  
Vol 11 (17) ◽  
pp. 6300-6310 ◽  
Author(s):  
Amir A. Jazaeri ◽  
Christopher S. Awtrey ◽  
Gadisetti V.R. Chandramouli ◽  
Yao Eric Chuang ◽  
Javed Khan ◽  
...  

2011 ◽  
Vol 11 (2) ◽  
pp. 287-292 ◽  
Author(s):  
Xiang Chen ◽  
Tong-Tao Yang ◽  
Xiu-Chun Qiu ◽  
Zhen-Gang Ji ◽  
Cun-Xiao Li ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2277
Author(s):  
Kenji Saito ◽  
Maiko Ito ◽  
Takuya Chiba ◽  
Huijuan Jia ◽  
Hisanori Kato

Many studies have shown the beneficial effects of calorie restriction (CR) on rodents’ aging; however, the molecular mechanism explaining these beneficial effects is still not fully understood. Previously, we conducted transcriptomic analysis on rat liver with short-term and mild-to-moderate CR to elucidate its early response to such diet. Here, we expanded transcriptome analysis to muscle, adipose tissue, intestine, and brain and compared the gene expression profiles of these multiple organs and of our previous dataset. Several altered gene expressions were found, some of which known to be related to CR. Notably, the commonly regulated genes by CR include nicotinamide phosphoribosyltransferase and heat shock protein 90, which are involved in declining the aging process and thus potential therapeutic targets for aging-related diseases. The data obtained here provide information on early response markers and key mediators of the CR-induced delay in aging as well as on age-associated pathological changes in mammals.


ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Margit L. H. Riis ◽  
Torben Lüders ◽  
Elke K. Markert ◽  
Vilde D. Haakensen ◽  
Anne-Jorun Nesbakken ◽  
...  

Gene expression studies on breast cancer have generally been performed on tissue obtained at the time of surgery. In this study, we have compared the gene expression profiles in preoperative tissue (core needle biopsies) while tumor is still in its normal milieu to postoperative tissue from the same tumor obtained during surgery. Thirteen patients were included of which eleven had undergone sentinel node diagnosis procedure before operation. Microarray gene expression analysis was performed using total RNA from all the samples. Paired significance analysis of microarrays revealed 228 differently expressed genes, including several early response stress-related genes such as members of the fos and jun families as well as genes of which the expression has previously been associated with cancer. The expression profiles found in the analyses of breast cancer tissue must be evaluated with caution. Different profiles may simply be the result of differences in the surgical trauma and timing of when samples are taken and not necessarily associated with tumor biology.


2017 ◽  
Author(s):  
Brian K. Lohman ◽  
William E. Stutz ◽  
Daniel I. Bolnick

AbstractSelection against migrants is key to maintaining genetic differences between populations linked by dispersal. Yet, migrants are not just passively weeded out by selection. Migrants may mitigate fitness costs by proactively choosing among available habitats, or by phenotypic plasticity. We previously reported that a reciprocal transplant of lake and stream stickleback (Gasterosteus aculeatus) found little support for divergent selection. We revisit that experiment to test whether phenotypic plasticity in gene expression may have helped migrants adjust to unfamiliar habitats. We measured gene expression profiles in stickleback via TagSeq and tested whether migrants between lake and stream habitats exhibited a plastic response to their new environment that allowed them to converge on the expression profile of adapted natives. We report extensive gene expression differences between genetically divergent lake and stream stickleback, despite gene flow. But for many genes, expression was highly plastic. Fish transplanted into the adjoining habitat partially converged on the expression profile typical of their new habitat. This suggests that expression plasticity may soften the impact of migration. Nonetheless, lake and stream fish differed in survival rates and parasite infection rates in our study, implying that expression plasticity is not fast or extensive enough to fully homogenize fish performance.


2010 ◽  
Vol 35 (3) ◽  
pp. 401-411 ◽  
Author(s):  
Bernd Kubista ◽  
Florian Klinglmueller ◽  
Martin Bilban ◽  
Martin Pfeiffer ◽  
Richard Lass ◽  
...  

2013 ◽  
Vol 25 (6) ◽  
pp. 966 ◽  
Author(s):  
M. E. Beltman ◽  
N. Forde ◽  
P. Lonergan ◽  
M. A. Crowe

The aim of the present study was to compare endometrial gene expression profiles in a group of beef heifers yielding viable or retarded embryos on Day 7 after oestrus as a means of potentially explaining differences in embryo survival rates. Heifers were classified as either: (1) viable, when the embryo collected on Day 7 after oestrus was at the correct developmental stage (i.e. morula/early blastocyst); or (2) retarded, when the embryo was arrested at the 2–16-cell stage. The focus of the present study was on genes that were associated with either the pro- or anti-inflammatory immune response. Endometrial gene expression was determined using quantitative real-time polymerase chain reaction analysis. Expression of the β-defensin (DEFB1), interferon (IFN)-α (IFNA), IFN-γ (IFNG), interleukin (IL)-6 (IL6), IL-10 (IL10), forkhead box P3 (FOXP3) and natural cytotoxicity triggering receptor 1 (NCR1) genes was lower in endometria from viable than retarded heifers. Expression of the nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (NKFB1), transforming growth factor (TGF)-β (TGFB), IFN-γ-inducible protein 16 (IFI16) and IL-21 (IL21) genes was higher in viable than retarded heifers. We propose that small disturbances in the expression of immune genes in the endometrium on Day 7 after oestrus can have detrimental effects on embryo survival.


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