Advances in nasopharyngeal carcinoma
Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. Current opinion in oncology
(Impact Factor: 4.47).
06/2008; 20(3):264-9. DOI: 10.1097/CCO.0b013e3282fad846
Nasopharyngeal carcinoma prognosis is related to its potential locoregional invasion and metastatic spread. Among prognostic factors, initial tumor-node-metastasis stage is the main one, besides other biological parameters. Worldwide development of positron emission tomography imaging is changing modalities of staging. Concomitant chemoradiotherapy represents one of the most recent advances in the treatment of nasopharyngeal carcinoma patients, besides intensity-modulated radiation therapy. This review updates these recent advances in diagnosis and treatment of nasopharyngeal carcinoma.
Recent publications have shown the superiority of fused positron emission tomography/computed tomography over positron emission tomography alone and conventional imaging to do an accurate staging and to impact on patient management. Circulating Epstein-Barr virus DNA load may be a useful prognostic marker in endemic regions. Recent meta-analysis confirmed the superiority of concurrent chemoradiotherapy to radiotherapy alone. Previous publications have shown that induction chemotherapy with new agents might be promising. Data demonstrating targeted therapies efficacy in metastatic nasopharyngeal carcinoma are limited to date.
Positron emission tomography-computed tomography is replacing conventional imaging in the initial M staging of nasopharyngeal carcinoma. Its usefulness in response evaluation after therapy and its place in the follow-up need to be prospectively evaluated. Cisplatin-based concomitant chemoradiotherapy is now the standard treatment for locally advanced patients. However, incidence of relapses remains high, and new multimodal therapy is needed.
Available from: Chien-Feng Li
- "Despite the fact that treatment is successful in the majority of the patients, challenges still exist, such as how to prevent a relapse of the disease, and how to treat patients with refractory or metastatic NPC (Razak et al., 2010). Identification of biomarkers that independently correlate with tumor aggressiveness will facilitate appropriate allocation of adjuvant therapy and will be valuable for patient-tailored strategy to manage high-risk NPCs (Guigay, 2008). Here, we demonstrate that TYMS represents such a marker. "
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ABSTRACT: Data mining on public domain identified that stathmin 1 (STMN1) transcript was significantly higher expressed in nasopharyngeal carcinoma (NPC). Also known as the oncoprotein 18, STMN1 performs an important function in regulating rapid microtubule remodeling of the cytoskeleton in response to the cellular conditions. Immunoexpression of STMN1 was retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The outcome was correlated with clinicopathological features and patient survivals. Results indicated that high STMN1 expressions (50 %) were correlated with advanced age (p = 0.027), higher T stage (p = 0.003), and overall clinical stage (p = 0.006) by the 7th American Joint Committee of Cancer Staging. In multivariate analyses, high STMN1 expression emerged as an independent prognosticator for worse disease-specific survival (p = 0.001), distal metastasis-free survival (p = 0.003), and local recurrence-free survival (p = 0.006). Exogenous expression of E2F transcription factor 1 (E2F1) or/and its dimeric partner, transcription factor Dp-1 (TFDP1), notably induced the STMN1 protein level in a NPC-derived cell line, TW01. Accordingly, high STMN1 protein level is commonly associated with adverse prognosticators and confers tumor aggressiveness in patients with NPC, and its upregulation might be attributed to E2F1 and/or TFDP1 transactivation.
Available from: PubMed Central
- "Most chemotherapies for NPC are cisplatin-based combinations ; therefore, we explored whether ZOL could enhance the cytotoxic activity of cisplatin. Considering that the peak serum concentrations of ZOL following 4 mg standard dose is approximately 1-2 μM before localization to the bone , 2 μM ZOL was used in combination with cisplatin at various concentrations. "
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ABSTRACT: Our recent cDNA microarray data showed that centromere protein F (CENP-F) is significantly upregulated in primary cultured nasopharyngeal carcinoma (NPC) tumor cells compared with normal nasopharyngeal epithelial cells. The goal of this study was to further investigate the levels of CENP-F expression in NPC cell lines and tissues to clarify the clinical significance of CENP-F expression in NPC as well as the potential therapeutic implications of CENP-F expression.
Real-time RT-PCR and western blotting were used to examine CENP-F expression levels in normal primary nasopharyngeal epithelial cells (NPEC), immortalized nasopharyngeal epithelial cells and NPC cell lines. Levels of CENP-F mRNA were determined by real-time RT-PCR in 23 freshly frozen nasopharyngeal biopsy tissues, and CENP-F protein levels were detected by immunohistochemistry in paraffin sections of 202 archival NPC tissues. Statistical analyses were applied to test for prognostic associations. The cytotoxicities of CENP-F potential target chemicals, zoledronic acid (ZOL) and FTI-277 alone, or in combination with cisplatin, in NPC cells were determined by the MTT assay.
The levels of CENP-F mRNA and protein were higher in NPC cell lines than in normal and immortalized NPECs. CENP-F mRNA level was upregulated in nasopharyngeal carcinoma biopsy tissues compared with noncancerous tissues. By immunohistochemical analysis, CENP-F was highly expressed in 98 (48.5%) of 202 NPC tissues. Statistical analysis showed that high expression of CENP-F was positively correlated with T classification (P < 0.001), clinical stage (P < 0.001), skull-base invasion (P < 0.001) and distant metastasis (P = 0.012) inversely correlated with the overall survival time in NPC patients. Multivariate analysis showed that CENP-F expression was an independent prognostic indicator for the survival of the patient. Moreover, we found that ZOL or FTI-277 could significantly enhance the chemotherapeutic sensitivity of NPC cell lines (HONE1 and 6-10B) with high CENP-F expression to cisplatin, although ZOL or FTI-277 alone only exhibited a minor inhibitory effect to NPC cells.
Our data suggest that CENP-F protein is a valuable marker of NPC progression, and CENP-F expression is associated with poor overall survival of patients. In addition, our data indicate a potential benefit of combining ZOL or FTI-277 with cisplatin in NPC suggesting that CENP-F expression may have therapeutic implications.
Available from: Srinivasan Dinesh Kumar
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ABSTRACT: The Y-Box-binding protein-1, a member of the cold-shock domain DNA- and RNA-binding protein superfamily, is known to mediate chemoresistance. The aim of this study was to determine the expression of Y-Box-binding protein-1 in nasopharyngeal cancer in vitro and in tumor tissue samples as well as analyze the clinicopathological significance of Y-Box-binding protein-1 expression in nasopharyngeal cancer, in particular as a predictor of outcome after treatment. The Y-Box-binding protein-1 expression profile was evaluated at the mRNA and protein levels in poorly differentiated CNE-2 nasopharyngeal cancer cells by real-time RT-PCR, western blot analysis and immunohistochemistry. Y-Box-binding protein-1 expression in 143 nasopharyngeal cancer specimens was examined by immunohistochemistry and correlated with clinicopathologic parameters. Y-Box-binding protein-1 mRNA and protein were found to be expressed in CNE-2 nasopharyngeal cancer cells in vitro. Of 143 patient tissue sections, 137 (96%) were stained positive for the Y-Box-binding protein-1 protein. Y-Box-binding protein-1 immunostaining was observed to be predominantly cytoplasmic. A higher recurrence of nasopharyngeal cancer was found in patients whose tissues had increased Y-Box-binding protein-1 expression (P<0.001). The Cox proportionate hazard regression model also established that high Y-Box-binding protein-1 immunoreactivity was significantly correlated with increased risk (2.13 times) of recurrence as compared to low Y-Box-binding protein-1 immunoreactivity (P=0.01). Within groups of patients treated by radiotherapy or chemoradiotherapy, recurrent cases had significantly higher Y-Box-binding protein-1 expression than nonrecurrent cases (P<0.001 and P=0.0035, respectively). These data suggest that Y-Box-binding protein-1 expression has clinicopathological significance with potential as a predictive marker of recurrence in nasopharyngeal cancer patients who undergo radiotherapy or chemoradiotherapy.
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