Chemosensitivity and p53–Bax pathway-mediated apoptosis in patients with uterine cervical cancer

Sultana, Habiba; Kigawa, Junzo; Kanamori, Yasunobu; Itamochi, Hiroaki; Oishi, Tsutomu; Sato, Shinya; Kamazawa, Shunji; Ohwada, Michitaka; Suzuki, Mitsuaki; Terakawa, Naoki

doi:10.1093/annonc/mdg071

Cited by 53 publications

(32 citation statements)

References 32 publications

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“…Interestingly, concordance has been seen with HPV16 prevalence and p53 up-regulation in the tumors. It seems that in HPV positive tumors, at least one of the p53 alleles is in wild type state and its up-regulation might activate the G1/S checkpoint, along with induction of apoptosis of the differentiated cells, as evident from previous studies (Sultana et al, 2003;Mitra et al, 2007). This induction might be due to the up-regulation of BAX by p53, as concordance has been seen between expressions of these proteins in post-therapy tumors.…”

Section: Discussionsupporting

confidence: 53%

Reduction of Proliferation and Induction of Apoptosis are Associated with Shrinkage of Head and Neck Squamous Cell Carcinoma due to Neoadjuvant Chemotherapy

Sarkar

Maiti²,

Jha³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Neoadjuvant chemotherapy (NACT) is a treatment modality whereby chemotherapy is used as the initial treatment of HNSCC in patients presenting with advanced cancer that cannot be treated by other means. It leads to shrinkage of tumours to an operable size without significant compromise to essential oro-facial organs of the patients. The molecular mechanisms behind shrinkage due to NACT is not well elucidated. Materials and Methods: Eleven pairs of primary HNSCCs and adjacent normal epithelium, before and after chemotherapy were screened for cell proliferation and apoptosis. This was followed by immunohistochemical analysis of some cell cycle (LIMD1, RBSP3, CDC25A, CCND1, cMYC, RB, pRB), DNA repair (MLH1, p53) and apoptosis (BAX, BCL2) associated proteins in the same set of samples. Results: Significant decrease in proliferation index and increase in apoptotic index was observed in post-therapy tumors compared to pre-therapy. Increase in the RB/ pRB ratio, along with higher expression of RBSP3 and LIMD1 and lower expression of cMYC were observed in post-therapy tumours, while CCND1 and CDC25A remained unchanged. While MLH1 remained unchanged, p53 showed higher expression in post-therapy tumors, indicating inhibition of cell proliferation and induction of apoptosis. Increase in the BAX/BCL2 ratio was observed in post-therapy tumours, indicating up-regulation of apoptosis in response to therapy. Conclusions: Thus, modulation of the G1/S cell cycle regulatory proteins and apoptosis associated proteins might play an important role in tumour shrinkage due to NACT.

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Section: Discussionsupporting

confidence: 53%

Reduction of Proliferation and Induction of Apoptosis are Associated with Shrinkage of Head and Neck Squamous Cell Carcinoma due to Neoadjuvant Chemotherapy

Sarkar

Maiti²,

Jha³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…This association between tumor proliferative activity and response to chemotherapy has been reported in breast cancer (27,28). Additionally, in cervical cancer, Sultana et al (29) reported that high expression of Ki-67 in preoperative biopsies was associated with the clinical response to platinum-containing neoadjuvant chemotherapy and improved prognosis. On the other hand, Costa et al (30) reported that there was no correlation between Ki-67 expression and clinical response to neoadjuvant chemotherapy or prognosis.…”

Section: Hdra Developed By Hoffman Et Almentioning

confidence: 54%

“…However, contradictory results have also been found in terms of Bcl-2 expression and patient prognosis (42)(43)(44)(45)(46)(47)(48)(49). Furthermore, in one study, no significant association was observed between Bcl-2 expression and the clinical effects of neoadjuvant chemotherapy (29). Thus, the association between Bcl-2 expression and chemosensitivity/radiosensitivity or prognosis has not been precisely defined.…”

Section: Hdra Developed By Hoffman Et Almentioning

confidence: 98%

“…In addition, the association between p53 overexpression and radiation sensitivity or sensitivity to platinum-containing chemotherapy have not been clearly defined in cervical cancer. Sultana et al (29) reported that there was no correlation between p53 expression in tumors and the clinical effects of platinum-containing chemotherapy. In the current study, a significant difference in p53 expression (LI) was observed between the high-and low-NDP sensitivity groups.…”

Section: Hdra Developed By Hoffman Et Almentioning

confidence: 99%

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Factors affecting platinum sensitivity in cervical cancer

et al. 2015

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Abstract. The present study aimed to investigate the association between nedaplatin (NDP) sensitivity and the expression of biological factors in cervical cancer. A total of 45 cervical cancer specimens, including 18 pretreatment biopsies and 27 surgical specimens, were used in histoculture drug response assays to determine the chemosensitivity of cervical cancer specimens to NDP. Each specimen was assessed for immunohistochemical expression of Ki-67, p53, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3, cyclooxygenase-2 (COX-2), and excision repair cross-complementation group 1 (ERCC1). The results revealed that low or negative expression of p53, Bcl-2 and COX-2, and high or positive expression of cleaved caspase-3 were significantly correlated with high sensitivity to NDP. However, there were no significant differences in Ki-67, Bax or ERCC1 expression between the low and high sensitivity groups. These findings indicate that sensitivity to platinum may be easily predicted by immunostaining for the detection of these specific factors in pretreatment biopsies or surgical specimens. The expression profiles of these targets may therefore provide additional information for planning individualized chemotherapy in the treatment of cervical cancer.

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“…Bcl-2, an anti-apoptotic protein, is an oncogene that inhibits radiation-or chemotherapy-induced apoptosis (30). Cervical cancers with Bcl-2 expression have been reported to exhibit radiation resistance and poor prognosis (31,32). Bax is a member of the Bcl-2 family and serves a role in enhancing apoptosis (33).…”

Section: Discussionmentioning

confidence: 99%

Regulation of cytotoxicity and apoptosis-associated pathways contributes to the enhancement of efficacy of cisplatin by baicalein adjuvant in human A549 lung cancer cells

et al. 2017

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Abstract. Scutellaria baicalensis (SB; Chinese name, huangqin) is widely used in Chinese medicine as a traditional adjuvant in the chemotherapy of lung and liver cancer. Baicalein is one of the bioactive flavonoid components isolated from the root of SB. The present study aimed to observe the effect of baicalein, in combination with platin-based systemic chemotherapy (cisplatin), on cytotoxicity and apoptosis of human A549 lung cancer cells. The cell cultures were treated with baicalein, cisplatin, or a combination of the two. Cell viability and cytotoxicity was assayed by XTT, and cell apoptosis was measured by flow cytometry. The apoptosis-associated proteins were detected by western blot analysis. The cytokines in the culture supernatant were detected by ELISA. The present study revealed that cisplatin and the baicalein-cisplatin combination inhibited viability and promoted cytotoxicity of A549 cells. Cisplatin, baicalein and baicalein-cisplatin combination treatments were effective in the promotion of apoptosis of A549 cells. Baicalein and baicalein-cisplatin combination treatments also inhibited B cell lymphoma-2 (Bcl-2) and increased Bcl-2-associated X protein (Bax) expression. Additionally, cisplatin, baicalein and the baicalein-cisplatin combination promoted caspase-3 expression. Furthermore, the baicalein-cisplatin combination suppressed the secretion of interleukin-6, and baicalein and the combination of baicalein cisplatin decreased the secretion of tumor necrosis factor-α of A549 cells. The present study concluded that baicalein combined with cisplatin induced cytotoxicity and apoptosis of A549 cells, and such activity may be associated with the regulation of Bcl-2, Bax and caspase-3, indicating a promising alternative method for lung cancer.

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Chemosensitivity and p53–Bax pathway-mediated apoptosis in patients with uterine cervical cancer

Abstract: Chemosensitivity in cervical cancer may be associated with apoptosis via the p53-Bax pathway.

Cited by 53 publications

References 32 publications

Reduction of Proliferation and Induction of Apoptosis are Associated with Shrinkage of Head and Neck Squamous Cell Carcinoma due to Neoadjuvant Chemotherapy

Reduction of Proliferation and Induction of Apoptosis are Associated with Shrinkage of Head and Neck Squamous Cell Carcinoma due to Neoadjuvant Chemotherapy

Factors affecting platinum sensitivity in cervical cancer

Regulation of cytotoxicity and apoptosis-associated pathways contributes to the enhancement of efficacy of cisplatin by baicalein adjuvant in human A549 lung cancer cells

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