Relationship between cyclin D1 expression and poor radioresponse of murine carcinomas

Milas, Luka; Akimoto, Tetsuo; Hunter, Nancy; Mason, Kathy; Buchmiller, Lara; Yamakawa, Michitaka; Muramatsu, Hiroyuki; Ang, K. Kian

doi:10.1016/s0360-3016(01)02693-1

Cited by 49 publications

(28 citation statements)

References 28 publications

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“…34 Besides independent early radio response pathways of p53 and NFB, recent evidences indicate collaboration between p53 and NFB pathways in radio response that aggravates the associated complexity. 35 Unlike p16, cyclin D1 is a downstream target of many radio responsive proteins like NFB, 34 and EGFR, 36 which may be the reason why it differentially affects radiotherapy response.…”

Section: Adenoviral P16mentioning

confidence: 99%

p53, p16 and cyclin D1: Molecular determinants of radiotherapy treatment response in oral carcinoma

Jayasurya

Francis

Kannan

et al. 2004

Intl Journal of Cancer

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Management of oral cancer by radiotherapy has witnessed promising advances in the past few years, with patient-tailored radio fractionation regimens. Different fractionation schedules, conventional and altered regimes, have been used in curative radiotherapy. Although contribution of biological markers on radio response has been evaluated, its unique influence on various radio fractionation schemes has not been accounted so far. Our study analyses a set of proteins that previously demonstrated radio response influence for their possible prognostic value in decision-making process between the respective fractionation schemes. Expression patterns of regulatory proteins such as p53, cyclin D1, p16, Cdk4, p21, Rb, bcl-2 and PCNA were determined by immunohistochemistry utilizing monoclonal antibodies in 125 patients who received curative radiotherapy dose. Among these 125 patients, 90 (72%) received altered fractionation, whereas 35 (28%) received conventional fractionation. p53 over-expression correlated with local treatment failure among the patients treated with conventional fractionation whereas cyclin D1 over-expression and p16 underexpression were associated with local treatment failure as well as overall survival in altered fractionation treated cases. Our findings suggest that wild-type p53 status may be an important parameter for achieving high local control in those patients undergoing conventional fractionation, where as intact p16 and cyclin D1 status may be beneficial for effective local control in patients who are treated with altered fractionation. Furthermore, it can be assumed that conventional fractionation employs p53-mediated apoptosis, whereas altered fractionation activates the functional G1 cell-cycle checkpoint for tumor growth suppression.

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Section: Adenoviral P16mentioning

confidence: 99%

p53, p16 and cyclin D1: Molecular determinants of radiotherapy treatment response in oral carcinoma

Jayasurya

Francis

Kannan

et al. 2004

Intl Journal of Cancer

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“…However, Jirawatnotai et al (2011) found that after the depletion of the human tumor cyclin D1 levels in mice missing pRb, the cells became more sensitive to radiation and DNA damage factors. Milas et al (2002) also found that the expression levels of cyclin D1 were negatively correlated with tumor radiosensitivity. These studies suggested that the cyclin D1 protein was closely related to the radiosensitivity of the tumor.…”

Section: Discussionmentioning

confidence: 86%

Association of cyclin D1 and survivin expression with sensitivity to radiotherapy in patients with nasopharyngeal carcinoma

Lin

et al. 2014

Genet. Mol. Res.

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ABSTRACT. The association between cyclin D1 and survivin protein expressions with radiotherapy sensitivity in patients with nasopharyngeal carcinoma was investigated. Biopsy specimens of 72 patients with nasopharyngeal carcinoma were collected before the initiation of radiotherapy (49 cases were in the radiationsensitive group and 23 cases were in the radiation-insensitive group). Conventional hematoxylin and eosin staining was used for tissue typing. The immunohistochemical SP method was used to detect cyclin D1 and survivin protein expression levels. The IBM SPSS Statistics 20 statistical software was applied for conducting the chi-squared test and the Spearman correlation analysis. In the 72 cases, the high expression rates of cyclin D1 were 28.6% (14/49) and 69.6% (16/23) in the radiotherapy-sensitive group and in the radiotherapy-insensitive group, respectively, and the differences between groups were statistically significant (P < 0.05). The high expression rates of survivin were 34.7% (17/49) and 73.9% (17/23) in the radiotherapy-sensitive group and in the radiotherapy-insensitive group, respectively, which differed significantly (P < 0.05). The protein expressions of cyclin D1 and survivin were positively correlated (Spearman's r = 0.353, P < 0.05). Cyclin D1 and survivin expression levels were negatively correlated with the radiosensitivity of nasopharyngeal carcinoma. Cyclin D1 and survivin may be used as molecular markers to predict the sensitivity of radiotherapy.

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“…The TCD 50 value of the GL261 tumor model, compared with the TCD 50 values of the other tumor models, are summarized in Table 3. [26][27][28][29][30][31] The TCD 50 values ranged from relatively radiosensitive (six of 16 tumor models had values between 42.9-58.3 Gy) to highly radioresistant (4 of 16 tumor models had values between 75.2-83.1 Gy). The radiosensitivity of the GL261 glioma tumor model was intermediate (5 of 16 tumor models had values between 62.3-67.6 Gy).…”

Section: Discussionmentioning

confidence: 99%

Radiation Sensitivity of GL261 Murine Glioma Model and Enhanced Radiation Response by Flavopiridol

Newcomb¹,

Lymberis²,

Lukyanov³

et al. 2005

Cell Cycle

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Response of a solid tumor to radiation treatment depends, in part, on the intrinsic radiosensitivity of tumor cells, the proliferation rate of tumor cells between radiation treatments and the hypoxic state of the tumor cells. A successful radiosensitizing agent would target S-phase cells and hypoxia. Recently, we demonstrated the anti-tumor effects of flavopiridol in the GL261 murine glioma model might involve (1) recruitment of tumor cells to S-phase (Newcomb et al., Cell Cycle 2004; 3:230-4) and (2) an anti-angiogenic effect on the tumor vasculature by downregulation of hypoxia-inducible factor-1α (HIF-1α) (Newcomb et al., Neuro-Oncology 2005; 7:225-35). Given that flavopiridol has demonstrated radiosensitizing activity in several murine tumor models, we tested whether it would enhance the response of GL261 tumors to radiation. In the present study, we evaluated the intrinsic radiation sensitivity of the GL261 glioma model using the tumor control/cure dose of radiation assay (TCD 50 ). We found that a single dose of 65 Gy (CI 57.1-73.1) was required to cure 50% of the tumors locally. Using the tumor growth delay assay, fractionated radiation (5 fractions of 5 Gy over 10 days) combined with flavopiridol (5 mg/kg) given three times weekly for three cycles produced a significant growth delay. Our results indicate that the GL261 murine glioma model mimics the radioresistance encountered in human gliomas, and thus should prove useful in identifying promising new investigational radiosensitizers for use in the treatment of glioma patients.

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Relationship between cyclin D1 expression and poor radioresponse of murine carcinomas

Cited by 49 publications

References 28 publications

p53, p16 and cyclin D1: Molecular determinants of radiotherapy treatment response in oral carcinoma

p53, p16 and cyclin D1: Molecular determinants of radiotherapy treatment response in oral carcinoma

Association of cyclin D1 and survivin expression with sensitivity to radiotherapy in patients with nasopharyngeal carcinoma

Radiation Sensitivity of GL261 Murine Glioma Model and Enhanced Radiation Response by Flavopiridol

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