Factors affecting platinum sensitivity in cervical cancer

Abstract

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.

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

“…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).…”

Cervical Carcinoma: Oncobiology and Biomarkers

“…HPV DNA, E6/E7 mRNA p53, Rb, p16INK4a, telomerase RNA gene (TERC), serum SCC-Ag, OCVA1 [8,[10][11][12][13]15,[20][21][22][23][24][25][26] Markers of cell cycle and proliferation Ki-67, cyclin D1, p53, p63 [12,[26][27][28][29][30][31][32][33][34][35][36] Markers of apoptosis P53, BCL-2, BCL-XL, BAX [10,27,[37][38][39][40][41][42][43][44] Expression of cytokeratins-markers of differentiation CK7, CK8, CK17, CK19 [27,36,37,[45][46][47][48][49] Markers of cell adhesion, invasion and metastasis E-cadherin, P-cadherin, CD44, ADAM9, MT1-MMP, TIMP-1, TIMP-2, MT1-MMP, MMP-2, MMP-1, MMP-9, MMP-14, proMMP-14 furin, gelatinase, TIMP-1 and TIMP-2 [27,[50][51][52]…”

“…According to data, susceptibility to platinum can be predicted by immunostaining for these specific factors in biopsies or surgical specimens before treatment, and expression profiles of these markers may provide additional information for planning individual chemotherapy for cervical cancer. Thus, individualized chemotherapy to maximize the effectiveness of treatment may become clinically valuable in the cases of cervical cancer [41]. Negative correlation of the expression profile of the anti-apoptotic proteins SAG, Bcl-xL, and p53 with the overall survival of patients with cervical cancer stages IIB-IVA has been demonstrated.…”

Development of machine learning models integrating PET/CT radiomic and immunohistochemical pathomic features for treatment strategy choice of cervical cancer with negative pelvic lymph node by mediating COX-2 expression

“…Previous studies have indicated elevated COX-2 was strongly related to LNM in stage IB cervical cancer (Kang et al, 2006), the high COX expression has been revealed positive correlation with malignancy in the parametrial tumor tissue or LNM (Ryu et al, 2000). Other studies also found that high-level expression of COX-2 was correlated with a poorer prognosis, recurrence, low sensitivity of nedaplatin, and radiosensitivity (Kim et al, 2003;Chen et al, 2005;Ishikawa et al, 2006;Manchana et al, 2006;Jo et al, 2007;Huang et al, 2013;Stasinopoulos et al, 2013;Kato et al, 2015). In neoplasia, COX-2 stimulates cell proliferation which promotes angiogenesis through pathways involving an increase in VEGF production (Huang et al, 2013;Xu et al, 2014).…”