Loss of p21 expression is associated with p53 mutations and increased cell proliferation and p27 expression is associated with apoptosis in maxillary sinus squamous cell carcinoma

Bandoh, Nobuyuki; Hayashi, Tatsuya; Takahara, Miki; Kishibe, Kan; Ogino, Takeshi; Katayama, Akihiro; Nonaka, Satoshi; Harabuchi, Yasuaki

doi:10.1080/00016480410023056

Cited by 13 publications

(7 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More interestingly, for the first time, we have found that GUTK specifically restored p21Waf1/Cip1 and p27Kip1 levels in colon cancer cells to the levels in normal colon cells. Previous studies have shown that lack of p21Waf1/Cip1 expression in tumors was correlated with higher proliferation and advanced tumor grade in human tumor biopsies and p21Waf1/Cip1 expression was correlated with prolonged disease‐free survival and more favorable outcomes in patients 29, 30. On the other hand, maxillary sinus squamous cell carcinoma and high‐grade breast cancer tumors with high p21Waf1/Cip1 or p27Kip1 levels demonstrated higher apoptotic indices 29, 31.…”

Section: Discussionmentioning

confidence: 96%

“…Previous studies have shown that lack of p21Waf1/Cip1 expression in tumors was correlated with higher proliferation and advanced tumor grade in human tumor biopsies and p21Waf1/Cip1 expression was correlated with prolonged disease-free survival and more favorable outcomes in patients. 29,30 On the other hand, maxillary sinus squamous cell carcinoma and high-grade breast cancer tumors with high p21Waf1/Cip1 or p27Kip1 levels demonstrated higher apoptotic indices. 29,31 Although p21Waf1/Cip1 is a CDK inhibitor, recent evidence suggested that it may play a role in apoptosis induced by TNF-family of death receptors and may also interact with or regulate the DNA repair mechanisms to induce apoptosis, especially in cells with mutated or nonfunctional p53.…”

Section: Discussionmentioning

confidence: 99%

“…29,30 On the other hand, maxillary sinus squamous cell carcinoma and high-grade breast cancer tumors with high p21Waf1/Cip1 or p27Kip1 levels demonstrated higher apoptotic indices. 29,31 Although p21Waf1/Cip1 is a CDK inhibitor, recent evidence suggested that it may play a role in apoptosis induced by TNF-family of death receptors and may also interact with or regulate the DNA repair mechanisms to induce apoptosis, especially in cells with mutated or nonfunctional p53. 32 Therefore, the selective up-regulation of p21Waf1/Cip1 by GUTK in p53mutated HT-29 cells may not only induce G 0 /G 1 cell cycle arrest, but may also be responsible for apoptosis.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1‐mediated G₀/G₁ cell cycle arrest and apoptosis

Kan

Yin

Hong

et al. 2012

Intl Journal of Cancer

View full text Add to dashboard Cite

Low selectivity is one of the major problems of currently used anticancer drugs, therefore, there is a high demand for novel, selective antitumor agents. In this study, the anticancer effects and mechanisms of guttiferone K (GUTK), a novel polyprenylated acylphloroglucinol derivative isolated from Garcinia cowa Roxb., were examined for its development as a novel drug targeting colon cancer. GUTK concentration- and time-dependently reduced the viability of human colon cancer HT-29 cells (IC(50) value 5.39 ± 0.22 μM) without affecting the viability of normal human colon epithelial CCD 841 CoN cells and induced G(0) /G(1) cell cycle arrest in HT-29 cells by down-regulating cyclins D1, D3 and cyclin-dependent kinases 4 and 6, while selectively restoring p21Waf1/Cip1 and p27Kip1 to levels comparable to those observed in normal colon cells, without affecting their levels in normal cells. GUTK (10.0 μM) induced cleavage of PARP, caspases-3, -8 and -9 and chromatin condensation to stimulate caspase-3-mediated apoptosis. The addition of a JNK inhibitor, SP600125, partially reversed GUTK-induced caspase-3 activity, indicating the possible involvement of JNK in GUTK-induced apoptosis. Furthermore, GUTK (10 mg/kg, i.p.) significantly decreased the tumor volume in a syngeneic colon tumor model when used alone or in combination with 5-fluorouracil without toxicity to the mice. Immunohistochemical staining of the tumor sections revealed a mechanism involving an increase in cleaved caspase-3 and a decrease in cell proliferation marker Ki-67. Our results support GUTK as a promising novel, potent and selective antitumor drug candidate for colon cancer.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1‐mediated G₀/G₁ cell cycle arrest and apoptosis

Kan

Yin

Hong

et al. 2012

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…In a study conducted using samples collected from 122 HCC patients after tumor resection, Kao [15] reported that HCC patients with negative expression of p21/WAF1 exhibited a poorer survival rate than the HCC patients with positive expression of p21/WAF1, suggesting that the expression of p21/WAF1 in HCC was a survival prognostic factor. MDM2 was rarely reported to be a prognostic factor in HCC, but was often reported in the maxillary sinus squamous cell carcinoma [33], in Egyptian esophageal carcinoma [34], in breast carcinoma [35], prostate adenocarcinoma [36], gastric cancer [37,38], and epithelial ovarian cancer [39,40]. …”

Section: Discussionmentioning

confidence: 99%

Correlation between expression of p53, p21/WAF1, and MDM2 proteins and their prognostic significance in primary hepatocellular carcinoma

Zhang

et al. 2009

J Transl Med

View full text Add to dashboard Cite

BackgroundTumor Protein p53 (p53), cyclin-dependent kinase inhibitor 1A (p21/WAF1), and murine double minute 2 (MDM2) participate in the regulation of cell growth. Altered expression of these gene products has been found in malignant tumors and has been associated with poor prognosis. Our aim was to investigate the expression of the 3 proteins in hepatocellular carcinoma (HCC) and their prognostic significance.MethodsWe examined p53, p21/WAF1, and MDM2 expression in 181 pairs of HCC tissues and the adjacent hepatic tissues by performing immunohistochemistry and examined the expression of the 3 proteins in 7 pairs of HCC tissues and the adjacent hepatic tissues by using western blot analysis.ResultsThe expression of p53, p21/WAF1, and MDM2 in the HCC tissues was significantly higher than those in the adjacent hepatic tissues (P < 0.05). A statistical correlation was observed between p53 and p21/WAF1 expression in HCC tissues (R = 0.195, P = 0.008). A statistical correlation was observed between expression of p53 and p21/WAF1 (R = 0.380, P = 0.000), p53 and MDM2 (R = 0.299, P = 0.000), p21/WAF1 and MDM2 (R = 0.285, P = 0.000) in 181 liver tissues adjacent to the tumor. Patients with a low pathologic grade HCC (I+II) had a higher tendency to express p53 on tumor cells than the patients with high pathologic grade HCC (III+IV) (P = 0.007). Survival analysis showed that positive p21/WAF1 expression or/and negative MDM2 expression in HCC was a predictor of better survival of patients after tumor resection (P < 0.05).ConclusionsThe proteins p53, p21/WAF1, and MDM2 were overexpressed in all the HCC cases in this study, and p53 and p21/WAF1 overexpression were positively correlated. The expression of p21/WAF1 and MDM2 can be considered as 2 useful indicators for predicting the prognosis of HCC.

show abstract

“…Previous studies have shown that lack of p21Waf1/Cip1 expression in tumors was correlated with higher proliferation and advanced tumor grade in human tumor biopsies and p21Waf1/Cip1 expression was correlated with prolonged disease‐free survival and more favorable outcomes in patients 29, 30. On the other hand, maxillary sinus squamous cell carcinoma and high‐grade breast cancer tumors with high p21Waf1/Cip1 or p27Kip1 levels demonstrated higher apoptotic indices 29, 31. Although p21Waf1/Cip1 is a CDK inhibitor, recent evidence suggested that it may play a role in apoptosis induced by TNF‐family of death receptors and may also interact with or regulate the DNA repair mechanisms to induce apoptosis, especially in cells with mutated or nonfunctional p53 32.…”

Section: Discussionmentioning

confidence: 96%

Efficacy, safety, and effects on blood pressure of naproxcinod 750 mg twice daily compared with placebo and naproxen 500 mg twice daily in patients with osteoarthritis of the hip: A randomized, double‐blind, parallel‐group, multicenter study

Baerwald

Verdecchia²,

Duquesroix³

et al. 2010

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To test the superiority of naproxcinod compared with placebo in relieving the signs and symptoms of hip osteoarthritis and to assess the safety of naproxcinod and its effects on blood pressure.Methods. In a 13-week, randomized, double-blind, parallel-group, multicenter study, 810 patients were randomized to receive either naproxcinod 750 mg twice daily, placebo, or naproxen 500 mg twice daily (2:2:1). Primary efficacy analyses compared naproxcinod and placebo using an analysis of covariance for 3 co-primary end points (the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] pain and function subscales and patient's overall rating of disease status). Safety assessments included adverse events and in-office blood pressure measurements.Results. The least squares mean changes from baseline were significantly greater with naproxcinod than with placebo (P < 0.0001) and were similar to those with naproxen at week 13 for the WOMAC pain score (؊25.81, ؊17.97, and ؊24.31 mm, respectively), the WOMAC function score (؊22.24, ؊13.45, and ؊21.67 mm, respectively), and patient's rating of disease status (0.86, 0.51, and 0.82, respectively). Changes from baseline in systolic blood pressure were similar in the naproxcinod and placebo groups at weeks 2, 6, and 13 (differences between groups of 0.25, ؊0.45, and ؊0.11 mm Hg, respectively). Changes in the naproxen group were greater than those in the placebo group (differences of 3.11, 3.03, and 2.00 mm Hg, respectively). Systolic blood pressure increases >10 mm Hg from baseline to week 13 occurred in 13.3%, 15.0%, and 20.3% of patients receiving naproxcinod, placebo, and naproxen, respectively. Naproxcinod and naproxen had similar adverse event and general safety profiles. Conclusion. The efficacy of naproxcinod for treating the signs and symptoms of hip osteoarthritis was statistically superior to that of placebo and similar to that of naproxen. Naproxcinod was well tolerated, with effects on systolic blood pressure similar to those of placebo.Osteoarthritis (OA) is the most common arthritic condition. It is estimated that half of all adults ages Ն65 years report symptoms of OA (1,2), and that up to 35 million people in Europe and 43 million people in the US may be affected (in the US, this number is expected to increase to ϳ59 million by 2020) (3,4). The prevalence of OA of the hip has been reported to be 0.9-7.4% ClinicalTrials.gov identifier: NCT00541489.

show abstract

Loss of p21 expression is associated with p53 mutations and increased cell proliferation and p27 expression is associated with apoptosis in maxillary sinus squamous cell carcinoma

Cited by 13 publications

References 22 publications

Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1‐mediated G₀/G₁ cell cycle arrest and apoptosis

Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1‐mediated G₀/G₁ cell cycle arrest and apoptosis

Correlation between expression of p53, p21/WAF1, and MDM2 proteins and their prognostic significance in primary hepatocellular carcinoma

Efficacy, safety, and effects on blood pressure of naproxcinod 750 mg twice daily compared with placebo and naproxen 500 mg twice daily in patients with osteoarthritis of the hip: A randomized, double‐blind, parallel‐group, multicenter study

Contact Info

Product

Resources

About

Loss of p21 expression is associated with p53 mutations and increased cell proliferation and p27 expression is associated with apoptosis in maxillary sinus squamous cell carcinoma

Cited by 13 publications

References 22 publications

Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1‐mediated G0/G1 cell cycle arrest and apoptosis

Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1‐mediated G0/G1 cell cycle arrest and apoptosis

Correlation between expression of p53, p21/WAF1, and MDM2 proteins and their prognostic significance in primary hepatocellular carcinoma

Efficacy, safety, and effects on blood pressure of naproxcinod 750 mg twice daily compared with placebo and naproxen 500 mg twice daily in patients with osteoarthritis of the hip: A randomized, double‐blind, parallel‐group, multicenter study

Contact Info

Product

Resources

About

Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1‐mediated G₀/G₁ cell cycle arrest and apoptosis

Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1‐mediated G₀/G₁ cell cycle arrest and apoptosis