Tumor specific gene expression profiles in human leiomyosarcoma

Shmulevich, Ilya; Hunt, Kelly K.; El‐Naggar, Adel K.; Taylor, Barry S.; Ramdas, Latha; Labordé, Pilar; Hess, Kenneth R.; Pollock, Raphael E.; Zhang, Wei

doi:10.1002/cncr.10425

Cited by 37 publications

(28 citation statements)

References 144 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Concerning the intratumor heterogeneity of GEP in other solid tumors, the degree of GEP variability within gastric cancer samples isolated from resection specimens of same patient was remarkably low (29). In surgically resected soft tissue sarcomas, the average intratumor distance was considerably shorter than the intertumor distance and intratumor heterogeneity seems to have only a small impact on the variability of GEP (30,31). In endoscopic biopsy samples of colorectal cancer, the intratumor heterogeneity of GEP is smaller than intertumor heterogeneity (21).…”

Section: Discussionmentioning

confidence: 96%

The feasibility of using biopsy samples from esophageal cancer for comprehensive gene expression profiling

Takemasa¹

2009

Int J Oncol

View full text Add to dashboard Cite

Abstract. Advanced esophageal cancer has been recently treated by multimodal therapy including preoperative chemotherapy or chemoradiotherapy and surgery. A biopsy sample provides a valuable specimen for understanding the biological characteristics of individual esophageal cancer. Pretreatment prediction of the response to chemotherapy or radiotherapy based on biological characteristics using biopsy samples is a desirable goal. In using biopsy samples for molecular analysis, there are two problems; the proportion of cancer cells and the intratumor heterogeneity. This study was conducted to investigate the feasibility of using endoscopic biopsy samples of esophageal squamous cell cancer (ESCC) for comprehensive gene expression profiling (GEP). Comprehensive GEP was performed in 40 bulky ESCC specimens and 10 normal esophageal epithelial specimens from patients who underwent esophageal resection and 52 endoscopic ESCC biopsy samples from 26 patients (two samples per one patient). Unsupervised hierarchical cluster analysis showed distinct profiles between the bulky ESCC specimens and normal epithelial specimens. Also, unsupervised hierarchical cluster analysis revealed distinct profiles between the biopsy ESCC samples and normal epithelial specimens. Moreover, a couple of biopsy samples taken from different locations of the same tumor were closely clustered together. That is, biopsy ESCC samples were distinguished from normal esophageal epithelial specimens and the intratumor heterogeneity of GEP was smaller than intertumor heterogeneity. GEP using biopsy ESCC samples is feasible and has the potential to represent the biological properties.

show abstract

Section: Discussionmentioning

confidence: 96%

The feasibility of using biopsy samples from esophageal cancer for comprehensive gene expression profiling

Takemasa¹

2009

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…Total RNA was isolated and quantified as described in ref. 23. Assays-onDemand from ABI (Applied Biosystems, Foster City, CA) were used to quantify RNA levels of OBSCN (Hs00405789 m1) and c9orf65 (Hs00373436 m1) on an ABI 7900 HT with a 96-well block.…”

Section: Methodsmentioning

confidence: 99%

Highly accurate two-gene classifier for differentiating gastrointestinal stromal tumors and leiomyosarcomas

Price

Trent

El‐Naggar³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

139

116

View full text Add to dashboard Cite

Gastrointestinal stromal tumor (GIST) has emerged as a clinically distinct type of sarcoma with frequent overexpression and mutation of the c-Kit oncogene and a favorable response to imatinib mesylate [also known as STI571 (Gleevec)] therapy. However, a significant diagnostic challenge remains in the differentiation of GIST from leiomyosarcomas (LMSs). To improve on the diagnostic evaluation and to complement the immunohistochemical evaluation of these tumors, we performed a whole-genome gene expression study on 68 well characterized tumor samples. Using bioinformatic approaches, we devised a two-gene relative expression classifier that distinguishes between GIST and LMS with an accuracy of 99.3% on the microarray samples and an estimated accuracy of 97.8% on future cases. We validated this classifier by using RT-PCR on 20 samples in the microarray study and on an additional 19 independent samples, with 100% accuracy. Thus, our two-gene relative expression classifier is a highly accurate diagnostic method to distinguish between GIST and LMS and has the potential to be rapidly implemented in a clinical setting. The success of this classifier is likely due to two general traits, namely that the classifier is independent of data normalization and that it uses as simple an approach as possible to achieve this independence to avoid overfitting. We expect that the use of simple marker pairs that exhibit these traits will be of significant clinical use in a variety of contexts.cancer ͉ classification ͉ diagnostic ͉ machine learning ͉ molecular signature G astrointestinal stromal tumors (GISTs) and leiomyosarcomas (LMSs) are common mesenchymal tumors with remarkably similar phenotypic features (1, 2). Until recently, the differentiation between these two entities had not been thought to be clinically relevant. Chemotherapeutic agents, such as doxorubicin and ifosfamide used in the treatment of soft-tissue sarcomas have resulted in response rates of 0-10% in patients with advanced GIST (3-5). However, the use of the selective tyrosine kinase inhibitor imatinib mesylate [also known as STI571 (Gleevec; Novartis Pharmaceuticals Corp., East Hanover, NJ)] has resulted in response rates of Ͼ50% for patients with GIST (6, 7, **). Conversely, patients with advanced LMS expect response rates of 27-53% when treated with doxorubicin or newer regimens combining gemcitabine with docetaxel (8, 9) but do not benefit from imatinib therapy (10, 11, † †). Thus, there is clear clinical importance in distinguishing between these two entities to guide the most effective therapy. Currently, the best marker to differentiate GIST from LMS is Kit immunostaining, which is subjective and variable due to cellular heterogeneity that may result in false-negative diagnoses. Kitnegative GISTs and Kit-expressing LMS have been reported on the basis of tumor cell morphology and other markers such as CD34, desmin, and smooth muscle actin ( ‡ ‡). The occurrence of Kit-negative GIST in the literature is Ϸ4-10% (2, 12). We used whole human genome microarray d...

show abstract

“…The construction, expression and purification of VEGF^i/rGel has been previously described (38). The fusion toxin was stored in sterile PBS at -20°C.…”

Section: Methodsmentioning

confidence: 99%

“…Cytotoxicity of VEGFoi/rGel and rGel against log phase PAE/KDR and PAE/Flt-1 cells have been previously described (38). Here, we assessed The results are expressed ± SEM.…”

Section: Methodsmentioning

confidence: 99%

“…Agents which prevent VEGF-A binding to its receptor, antibodies which directly block the KDR receptor itself and small molecules which block the kinase activity of the KDR and thereby block growth factor signaling are all under development (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). Recently, our laboratory reported the development of a growth factor fusion construct of VEGF121 and the recombinant toxin gelonin (rGel) (38). The rGel toxin is a single chain n-glycosidase similar in its action to ricin A chain (39).…”

Section: Internalization Of Vegfmmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of Novel Agents Which Target Neovasculature of Breast Tumors

Rosenblum¹

2005

View full text Add to dashboard Cite

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the lime for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Infonnatlon Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. and TITLE AND SUBTITLEEvaluation of Novel Agents which Target Neovasculature of Breast Tumors AUTHOR(S)Michael Rosenblum, Ph.D. FUNDING NUMBERSDAMD17-02-1-0457 PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)The ABSTRACT (Maximum 200 Words)The unique fusion toxin VEGFiji/rGel can specifically kill both log-phase and confluent vascular endothelial cells expressing the KDR receptor for VEGF (PNAS 99:7866,2002). We have discovered 19 unique genes upregulated{>5 fold) in endothelial cells treated with VEGFi2i/rGel(confirmed by Western and RT-PCR).VEGFi2i/rGel(i.v.) treatment had a dramatic cytotoxic effect in both orthotopic and metastatic human breast tumor models. Against the orthotopic model, tumor growth was signi'ficantly delayed by~50%. In addition, tumors completely regressed in 3/6 (50%) of treated mice. In the metastatic breast model, treatment with VEGFiji/rGel reduced both the number and area of lung foci by 58% and 50% respectively and we demonstrated VEGFi2i/rGel(by IHC) on lung tumor vasculature but not normal vasculature. In addition, the number of blood vessels per mm^ in metastatic foci was 198+ 37 versus 388-1-21 for treated and control respectively. Approximately 62% of metastatic colonies from the VEGF/rGel treated group had <10 vessels/colony compared to 23% in the control group. The fll<-l receptor on blood vessel endothelium was intensely expressed on control tumors, but not expressed on treated tumors. Metastatic foci had a 3 fold lower Ki-67 labeling index compared to control tumors. This suggests that VEGFi2i/rGel has impressive antitumor activity in breast cancer. SUBJECT TERMS Reportable Outcomes 16Conclusions 17 References 18Appendices 22 Evaluation of Novel Agents Which Target Neovasculature of Breast Tumors IntroductionBiological studies examining the development of the vascular tree in normal development and in disease states have identified numerous cytokines and their receptors responsible for triggering and maintaining this process (1-7). Tumor neovascularization is central not only to the growth and development of the primary lesion but appears to be a critical factor in the development and maintenance of metastases (8)(9)(10)(11)(12). Clinical studies in bladder cancer (9) have demonstrated a correlation between micro-vessel density and metastases. In addition, studies of breast cancer metastases by have demonstrated that microvessel coimt in primary tumors appears to be related to the presenc...

show abstract

Tumor specific gene expression profiles in human leiomyosarcoma

Cited by 37 publications

References 144 publications

The feasibility of using biopsy samples from esophageal cancer for comprehensive gene expression profiling

The feasibility of using biopsy samples from esophageal cancer for comprehensive gene expression profiling

Highly accurate two-gene classifier for differentiating gastrointestinal stromal tumors and leiomyosarcomas

Evaluation of Novel Agents Which Target Neovasculature of Breast Tumors

Contact Info

Product

Resources

About