ErbB‐2 expression is correlated with poor prognosis for patients with osteosarcoma

Onda, Masanori; Matsuda, Satoru; Higaki, Shogo; Iijima, Tadahiko; Fukushima, Jun‐ichi; Yokokura, Akira; Kojima, Tatsuyoshi; Horiuchi, Hajime; Kurokawa, Takahide; Yamamoto, Tadashi

doi:10.1002/(sici)1097-0142(19960101)77:1<71::aid-cncr13>3.3.co;2-l

Cited by 53 publications

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“…Some immunohistochemical studies demonstrated a significant correlation between Her-2/neu expression and a poor histologic response to preoperative chemotherapy, a decreased event-free survival as well as an increased risk of pulmonary metastases. [17][18][19]23 In contrast, other studies observed Her-2/neu expression irrespective of histologic subtype and grade that was not associated with response to preoperative chemotherapy and clinical outcome. 22 Further reports did not observe Her-2/neu overexpression or even reported complete absence of Her-2/neu Figure 5 RNA was extracted from the indicated numbers of lasermicrodissected cells obtained from a decalcified, paraffinembedded and formalin-fixed osteosarcoma section and converted to cDNA.…”

Section: Discussionmentioning

confidence: 85%

“…Besides morphological and biochemical markers like tumor volume and primary tumor site 6 as well as serum levels of lactate dehydrogenase and alkaline phosphatase, 1 genetic markers have also been investigated. Expression of P-glycoprotein 8 and Her-2/neu (erbB2) 18 have been correlated with tumor regression and clinical outcome but reports are controversial. Some immunohistochemical studies demonstrated a significant correlation between Her-2/neu expression and a poor histologic response to preoperative chemotherapy, a decreased event-free survival as well as an increased risk of pulmonary metastases.…”

Section: Discussionmentioning

confidence: 99%

“…Using immunohistochemical assays, some studies demonstrated Her-2/neu overexpression in osteosarcoma tissues, which strongly correlated with early pulmonary metastases, less tumor necrosis after preoperative chemotherapy and a significantly decreased event-free survival rate. [17][18][19] Other studies did not observe any Her-2/neu expression or only cytoplasmic expression 20 which is in contrast to membranous positivity considered as non-specific. In these studies, observation of cytoplasmic positivity was independent of histologic subtype and grade and not associated with response to preoperative chemotherapy or disease progression.…”

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confidence: 91%

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Evaluation of the predictive value of Her-2/neu gene expression on osteosarcoma therapy in laser-microdissected paraffin-embedded tissue

Fellenberg

Krauthoff

et al. 2003

Lab Invest

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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confidence: 91%

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Evaluation of the predictive value of Her-2/neu gene expression on osteosarcoma therapy in laser-microdissected paraffin-embedded tissue

Fellenberg

Krauthoff

et al. 2003

Lab Invest

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“…Because many of the receptors and downstream signaling molecules are tyrosine kinases [18,22], inhibitors of these kinases are a majority of the most promising anticancer drugs [4,10,21,27]. Although osteosarcoma has not been as well studied as other types of cancer, overexpression in osteosarcoma has been reported for both growth factors and their tyrosine kinase receptors, and overexpression of some of these molecules correlates with metastasis and poor survival in patients with osteosarcoma [5,8,9,15,17,20,23,28,33,36,47,49,60,65].…”

Section: Introductionmentioning

confidence: 99%

Specific Tyrosine Kinase Inhibitors Regulate Human Osteosarcoma Cells In vitro

Messerschmitt

Rettew

Brookover

et al. 2008

Clin Orthop Relat Res

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Inhibitors of specific tyrosine kinases are attractive lead compounds for development of targeted chemotherapies for many tumors, including osteosarcoma. We asked whether inhibition of specific tyrosine kinases would decrease the motility, colony formation, and/or invasiveness by human osteosarcoma cell lines (TE85, MNNG, 143B, SAOS-2, LM-7). An EGF-R inhibitor reduced motility of all five cell lines by 50% to 80%. In contrast, an IGF-1R inhibitor preferentially reduced motility by 42% in LM-7 cells and a met inhibitor preferentially reduced motility by 80% in MNNG cells. The inhibitors of EGF-R, IGF-1R, and met reduced colony formation by more than 80% in all tested cell lines (TE85, MNNG, 143B). The EGF-R inhibitor reduced invasiveness by 62% in 143B cells. The JAK inhibitor increased motility of SAOS-2 and LM7 cells without affecting colony formation or invasiveness. Inhibitors of HER-2, NGF-R, and PDGF-Rs did not affect motility, invasiveness, or colony formation. These results support the hypothesis that specific tyrosine kinases regulate tumorigenesis and/or metastasis in osteosarcoma.

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“…Clinical studies indicated that overexpression of HER2/neu correlated with poor prognosis, shorter patient survival, and chemoresistance. 5,6 We previously demonstrated that TC71 human Ewing's sarcoma cells overexpress HER2/neu. Thus, HER2/ neu may also play a role in the poor disease-free survival rate associated with multiagent chemotherapy in this disease.…”

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confidence: 99%

Adenovirus-E1A gene therapy enhances the in vivo sensitivity of Ewing's sarcoma to VP-16

et al. 2002

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This study determined the effect of Ad -E1A gene therapy in vivo. TC71 cells ( 2Â10 6 ) injected subcutaneously into nude mice resulted in tumor development ( 1 -3 mm ) 6 days later. Animals were then treated with Ad -E1A or Ad --gal ( 5Â10 9 plaque -forming units ) by intratumoral injection twice weekly for 2 weeks. Animals received 8 mg / kg VP -16 given by intraperitoneal injection daily for 5 days following the first week of treatment with Ad -E1A or Ad --gal. Control animals received no therapy or VP -16 only after tumor cells were injected. When tumors exceeded 2Â2 cm, the mice were sacrificed and the tumors underwent histologic and immunohistochemical analysis. Tumors from mice treated with Ad -E1A plus VP -16 were 9.6 -fold smaller than those treated with VP -16 alone and 6.3 -fold smaller than those treated with Ad -E1A alone. HER2 / neu p185 protein expression decreased in all tumors that received Ad -E1A therapy. TUNEL fluorescence staining revealed more apoptosis in the tumors from animals treated with Ad -E1A plus VP -16 than in those from animals treated with Ad -E1A alone, Ad --gal plus VP -16, or VP -16 alone. These data demonstrated that Ad -E1A gene therapy down -regulated HER2 / neu expression, increased tumor cell apoptosis induced by VP -16, and enhanced tumor cell sensitivity to VP -16. Ad -E1A may have potential in the treatment of relapsed drug -resistant Ewing's sarcoma. Cancer Gene Therapy ( 2002 ) 9, 407 -413 DOI: 10.1038 / sj / cgt / 7700449Keywords: Ewing's sarcoma; Ad -E1A; gene therapy; VP -16 E wing's sarcoma is the second most common primary malignant bone tumor in children and young adults and has a high potential for metastasizing to the lungs, bones, and bone marrow. Most patients with Ewing's sarcoma die from lung and bone metastases. The overall 5-year survival rate is 41.2%. 1,2 Moreover, the prognosis is poor for patients who have had a relapse and for patients with large primary tumors or metastatic disease at presentation. Therefore, new strategies are needed to improve the survival rates. The HER2/neu oncogene encodes a 185 -kDa human epidermal growth factor receptor-2 transmembrane protein ( p185 ) with intrinsic tyrosine kinase activity. Overexpression of HER2 /neu was found in approximately 30% of human breast and ovarian cancers. 3,4 Enhanced expression of HER2 /neu increased the tumorigenicity and metastatic potential of human ovarian and lung cancer cells. Clinical studies indicated that overexpression of HER2/neu correlated with poor prognosis, shorter patient survival, and chemoresistance. 5,6 We previously demonstrated that TC71 human Ewing's sarcoma cells overexpress HER2/neu. Thus, HER2/ neu may also play a role in the poor disease-free survival rate associated with multiagent chemotherapy in this disease. The adenovirus type 5 early region 1A (E1A ) gene is a wellknown transcriptional factor. This gene inhibits HER2 /neu expression in both rodent and human breast cancer and ovarian cancer cells through the HER2 /neu promoter and with the involvement of the H...

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ErbB‐2 expression is correlated with poor prognosis for patients with osteosarcoma

Cited by 53 publications

References 0 publications

Evaluation of the predictive value of Her-2/neu gene expression on osteosarcoma therapy in laser-microdissected paraffin-embedded tissue

Evaluation of the predictive value of Her-2/neu gene expression on osteosarcoma therapy in laser-microdissected paraffin-embedded tissue

Specific Tyrosine Kinase Inhibitors Regulate Human Osteosarcoma Cells In vitro

Adenovirus-E1A gene therapy enhances the in vivo sensitivity of Ewing's sarcoma to VP-16

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