Expression of cyclins, p53, and Ki-67 in cervical squamous cell carcinomas: overexpression of cyclin A is a poor prognostic factor in stage Ib and II disease

Shiohara, Shigeki; Shiozawa, Tanri; Miyamoto, Tsutomu; Feng, Yuemin; Kashima, Hiroyasu; Kurai, Makoto; Suzuki, Asuka; Konishi, Ikuo

doi:10.1007/s00428-005-1252-0

Cited by 26 publications

(25 citation statements)

References 36 publications

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“…In a second approach for determination of the proliferative activity, various antibodies to proliferation-associated antigens have been used to determine the proliferative activity of tumors 41,42. Of these antibodies, Ki-67, expressed in cycling cells, has gained considerable popularity for growth fraction determination.…”

Section: Discussionmentioning

confidence: 99%

Sildenafil potentiates the antitumor activity of cisplatin by induction of apoptosis and inhibition of proliferation and angiogenesis

El-Naa¹,

Othman²,

Younes³

2016

DDDT

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Sildenafil is the first phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction. However, recent studies have been suggesting an antitumor effect of sildenafil. The current study assessed the aforementioned activity of sildenafil in vivo and in vitro in solid-tumor-bearing mice and in a human cell line MCF-7, respectively. Moreover, we investigated the impact of sildenafil on cisplatin antitumor activity. The solid tumor was induced by inoculation of Ehrlich ascites carcinoma cells in female mice. The tumor-bearing mice were assigned randomly to control (saline), sildenafil (sildenafil 5 mg/kg/d, PO daily for 15 days), cisplatin (cisplatin 7.5 mg/kg, IP once on the 12th day of Ehrlich ascites carcinoma inoculation), and combination therapy (cisplatin and sildenafil) groups. The tumor volume was measured at the end of the treatment period along with the following parameters: angiogenin, vascular endothelial growth factor, tumor necrosis factor-α, Ki-67, caspase-3, DNA-flow cytometry analysis, and histopathological examination. The study results showed that sildenafil has significantly decreased the tumor volume by 30.4%, angiogenin and tumor necrosis factor-α contents, as well as vascular endothelial growth factor expression. Additionally, caspase-3 level significantly increased with sildenafil treatment, whereas Ki-67 expression failed to show any significant changes. Furthermore, the cell cycle analysis revealed that sildenafil was capable of improving the category of tumor activity from moderate to low proliferative. Sildenafil induced necrosis in the tumor. Moreover, the drug of interest showed cytotoxic activity against MCF-7 in vitro as well as potentiated cisplatin antitumor activity in vivo and in vitro. These findings shed light on the antitumor activity of sildenafil and its possible impact on potentiating the antitumor effect of conventional chemotherapeutic agents such as cisplatin. These effects might be related to antiangiogenic, antiproliferative, and apoptotic activities of sildenafil.

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Section: Discussionmentioning

confidence: 99%

Sildenafil potentiates the antitumor activity of cisplatin by induction of apoptosis and inhibition of proliferation and angiogenesis

El-Naa¹,

Othman²,

Younes³

2016

DDDT

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“…46 However, cyclin A was found to be a poor prognostic indicator for squamous cell carcinoma of the cervix. 19 In vulvar carcinoma, Ki67, but not cyclin A, has been found to be of prognostic value. 47,48…”

Section: Cyclin a And Ki67mentioning

confidence: 98%

Prognostic Significance of Cell Cycle- and Invasion-Related Molecular Markers and Genomic Instability in Primary Carcinoma of the Vagina

Hellman¹,

Johansson

Andersson

et al. 2013

Int J Gynecol Cancer

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“…The expression of Ki-67 and CD31 was assessed in various grades of cervical intraepithelial neoplasia (CIN) to evaluate their potential to predict the extent of possible damage to the epithelium and CIN progression. Ki-67, a non-histone protein with short half-life, is expressed in the nuclei of proliferating cells, becoming a marker of cell proliferation 44,45 . Angiogenesis is correlated with the potential for solid tumor metastasis.…”

Section: Referencesmentioning

confidence: 99%

PTEN expression in patients with carcinoma of the cervix and its association with p53, Ki-67 and CD31

Loures¹,

Cândido²,

Vidigal³

et al. 2014

Rev. Bras. Ginecol. Obstet.

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PURPOSE: To investigate protein expression and mutations in phosphatase and tensin homolog (PTEN) in patients with stage IB cervical squamous cell carcinoma (CSCC) and the association with clinical-pathologic features, tumor p53 expression, cell proliferation and angiogenesis. METHODS: Women with stage IB CSCC (n=20 -Study Group) and uterine myoma (n=20 -Control Group), aged 49.1±1.7 years (mean±standard deviation, range 27-78 years), were prospectively evaluated. Patients with cervical cancer were submitted to Piver-Rutledge class III radical hysterectomy and pelvic lymphadenectomy and patients in the Control Group underwent vaginal hysterectomy. Tissue samples from the procedures were stained with hematoxylin and eosin for histological evaluation. Protein expression was detected by immunohistochemistry. Staining for PTEN, p53, Ki-67 and CD31 was evaluated. The intensity of PTEN immunostaining was estimated by computer-assisted image analysis, based on previously reported protocols. Data were analyzed using the Student's t-test to evaluate significant differences between the groups. Level of significance was set at p<0.05. RESULTS: The PTEN expression intensity was lower in the CSCC group than in the Control (benign cervix) samples (150.5±5.2 versus 204.2±2.6; p<0.001). Our study did not identify any mutations after sequencing all nine PTEN exons. PTEN expression was not associated with tumor expression of p53 (p=0.9), CD31 (p=0.8) or Ki-67 (p=0.3) or clinical-pathologic features in patients with invasive carcinoma of the cervix. CONCLUSIONS: Our findings demonstrate that the PTEN protein expression is significantly diminished in CSCC.

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Expression of cyclins, p53, and Ki-67 in cervical squamous cell carcinomas: overexpression of cyclin A is a poor prognostic factor in stage Ib and II disease

Cited by 26 publications

References 36 publications

Sildenafil potentiates the antitumor activity of cisplatin by induction of apoptosis and inhibition of proliferation and angiogenesis

Sildenafil potentiates the antitumor activity of cisplatin by induction of apoptosis and inhibition of proliferation and angiogenesis

Prognostic Significance of Cell Cycle- and Invasion-Related Molecular Markers and Genomic Instability in Primary Carcinoma of the Vagina

PTEN expression in patients with carcinoma of the cervix and its association with p53, Ki-67 and CD31

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