<i>p</i>53 gene mutation and MDM2 overexpression in a case of primary malignant fibrous histiocytoma of the jejunum

Jiao, Yu‐Fei; Nakamura, Shinichi; Sugai, Tamotsu; Habano, Wataru; Uesugi, Noriyuki; Oikawa, Moriyasu; Sato, Tomoe

doi:10.1034/j.1600-0463.2002.100207.x

Cited by 4 publications

(2 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In MFH patients, the tumor tissues contained G → T transversions in the H‐ ras proto‐oncogene ( 15 ) and an exon of the p53 tumor suppressor gene. ( 16 ) These clinical studies support our findings, which show the formation of mutagenic DNA lesions to be mediated by the inflammatory responses that participate in the carcinogenesis of soft tissues. ROS are generated from multiple sources, including carcinogenic chemicals and their metabolites, and electron transport chain in mitochondria in addition to inflammation.…”

Section: Discussionmentioning

confidence: 76%

“…( 9,14 ) In MFH patients, the tumor tissues have been reported to have mutations in proto‐oncogenes and tumor suppressor genes. ( 15–17 ) We have previously performed clinical studies to examine the formation of 8‐nitroguanine and 8‐oxodG in patients with various inflammatory diseases. ( 18,19 ) We have discovered that these DNA lesions were specifically formed at sites of carcinogenesis under various inflammatory conditions.…”

mentioning

confidence: 99%

See 1 more Smart Citation

iNOS‐dependent DNA damage in patients with malignant fibrous histiocytoma in relation to prognosis

Hoki¹,

Hiraku²,

et al. 2006

Cancer Science

View full text Add to dashboard Cite

Malignant fibrous histiocytoma (MFH) is one of the most common soft tissue sarcomas. MFH has been proposed to be a lesion accompanied with inflammatory responses. During chronic inflammation, reactive nitrogen and oxygen species generated from inflammatory cells are considered to participate in carcinogenesis by causing DNA damage. 8-nitroguanine is a mutagenic nitrative DNA lesion formed during chronic inflammation. We examined whether nitrative DNA damage is related to the prognosis of MFH patients. We performed immunohistochemical analyses to examine the distribution of DNA damage and the expression of inflammation-related molecules including inducible nitric oxide synthase (iNOS), nuclear factor-κ κ κ κB (NF-κ κ κ κB), and cyclooxygenase-2 (COX-2) in clinical specimens from 25 patients with MFH. We also analyzed the correlation of DNA damage or the expression of these genes with the prognosis of MFH patients. Immunohistochemical staining revealed that the formation of 8-nitroguanine and 8-oxo-7,8-dihydro-2′ ′ ′ ′-deoxyguanosine (8-oxodG), an oxidative DNA lesion, occurred to a much greater extent in MFH tissue specimens from deceased patients than in live patients. iNOS, NF-κ κ κ κB and COX-2 were colocalized with 8-nitroguanine in MFH tissues. It is noteworthy that the statistical analysis using the Kaplan-Meier method demonstrated strong 8-nitroguanine staining to be associated with a poor prognosis. In conclusion, 8-nitroguanine appears to participate in not only the initiation and promotion of MFH, but also in the progression of MFH, and could therefore be used as a promising biomarker to evaluate the prognosis of cancer patients. (Cancer Sci 2007; 98: 163-168) M alignant fibrous histiocytoma has been regarded as one of the most common soft tissue sarcomas occurring in adult patients, (1) and it occurs most frequently in the extremities, trunk and retroperitoneum.(2) MFH is classified into four subtypes including storiform-pleomorphic (60 -70%), myxoid (10 -20%), giant cell (approximately 10%) and inflammatory (relatively rare).(3) MFH has been proposed to be a lesion accompanied with inflammatory responses. The expression of cytokines in a certain type of MFH (inflammatory MFH) may account for the local inflammatory infiltrate and the aggressive nature observed in these malignant cells.(4) In the early phases of experimentally induced rat sarcoma, an inflammatory reaction characterized by an infiltration of lymphocytes, monocytes and macrophages was observed.(5) It has been hypothesized that many malignancies arise from areas of inflammation.(6,7) Moreover, chronic inflammation has also been proposed to contribute to the development of various cancers.(6,7) These findings led us to an idea that the inflammatory responses thus play a role in the pathogenesis of MFH.During chronic inflammation, RNS and ROS are generated from inflammatory and epithelial cells, and therefore are considered to play a key role in both carcinogenesis and tumor progression. (8,9) ROS can induce the formation of 8-oxod), an indi...

show abstract

Section: Discussionmentioning

confidence: 76%

mentioning

confidence: 99%

iNOS‐dependent DNA damage in patients with malignant fibrous histiocytoma in relation to prognosis

Hoki¹,

Hiraku²,

et al. 2006

Cancer Science

View full text Add to dashboard Cite

show abstract

Diagnostic value of MDM2 RNA in situ hybridization for low-grade osteosarcoma: Consistency comparison of RNA in situ hybridization, fluorescence in situ hybridization, and immunohistochemistry

Chen

et al. 2023

Virchows Arch

View full text Add to dashboard Cite

Therapeutic Efficacy of p53 Restoration in Mdm2-Overexpressing Tumors

Zhang

El‐Naggar

et al. 2014

Molecular Cancer Research

View full text Add to dashboard Cite

The p53 (TP53) tumor suppressor is the most frequently mutated gene in human cancers. Restoring expression of wild-type p53 has led to tumor growth suppression in a variety of tumor models that are p53 deficient. Other mechanisms, e.g. up-regulation of Mdm2, exist in tumors to inactivate the p53 pathway. Mdm2, an E3 ubiquitin-ligase that targets p53 for proteasomal degradation, is present at high levels in many tumors with wild-type p53. In this study, the effects of restoring p53 activity were probed in Mdm2-overexpressing tumors genetically using animal models. Here it was demonstrated that elevated levels of Mdm2 and decreased levels of p53 act additively to dampen p53 activity in DNA damage response and tumor development. Our data further indicate that restoration of wild-type p53 expression in Mdm2-overexpressing angiosarcomas results in tumor stasis and regression in some cases. Finally, it was determined that restored p53 suppressed cell proliferation but did not elicit apoptosis in the Mdm2-overexpressing angiosarcomas.

show abstract

p53 gene mutation and MDM2 overexpression in a case of primary malignant fibrous histiocytoma of the jejunum

Cited by 4 publications

References 17 publications

iNOS‐dependent DNA damage in patients with malignant fibrous histiocytoma in relation to prognosis

iNOS‐dependent DNA damage in patients with malignant fibrous histiocytoma in relation to prognosis

Diagnostic value of MDM2 RNA in situ hybridization for low-grade osteosarcoma: Consistency comparison of RNA in situ hybridization, fluorescence in situ hybridization, and immunohistochemistry

Therapeutic Efficacy of p53 Restoration in Mdm2-Overexpressing Tumors

Contact Info

Product

Resources

About