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Nasopharyngeal carcinoma (NPC) is a head and neck cancer rare throughout most of the world but common in certain geographic areas, such as southern Asia. While environmental factors and genetic susceptibility play important roles in NPC pathogenesis, the Epstein-Barr virus in particular has been implicated in the molecular abnormalities leading to NPC. There is upregulation of cellular proliferation pathways such as the Akt pathway, mitogen-activated protein kinases, and the Wnt pathway. Cell adhesion is compromised due to abnormal E-cadherin and β-catenin function. Aberrations in cell cycle are due to dysregulation of factors such as p16, cyclin D1, and cyclin E. Anti-apoptotic mechanisms are also upregulated. There are multiple abnormalities unique to NPC that are potential targets for novel treatments. Keywordsnasopharyngeal carcinoma (NPC); Epstein; Barr virus (EBV); LMP1; tumorigenesis; review Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma that usually develops around the ostium of the Eustachian tube in the lateral wall of the nasopharynx. 1 Though rare among whites, NPC is particularly common in the southern Chinese population of Guangdong, Inuits of Alaska, and native Greenlanders. 2,3 Chinese emigrants continue to have a high incidence of the disease, but the rate of NPC among ethnic Chinese born in North America is considerably lower than those born in China. 4 This epidemiologic evidence implies that both environmental factors and genetic susceptibility play roles in the development of NPC. The environmental factors may include exposure to nitrosamines in salted and pickled foods. 5 Certain human leukocyte antigen subtypes have been associated with NPC, as they have various genetic polymorphisms. 6 The World Health Organization classifies NPC based on histology. 7 Type 1, keratinizing squamous carcinoma, is characterized by well-differentiated cells that produce keratin. Type 2, nonkeratinizing squamous carcinoma, varies in cell differentiation but does not produce keratin. Type 3 is also nonkeratinizing, but is less differentiated, with highly variable cell types (clear cell, spindle cell, anaplastic). Types 2 and 3 NPC are Epstein-Barr virus (EBV) Correspondence to: D. M. Jablons, jablonsd@surgery.ucsf.edu. Standard treatment for NPC is radiotherapy, but concurrent adjuvant chemotherapy improves survival rates. 10 As with other cancers, the prognosis of NPC depends upon tumor size, lymph node involvement, and distant metastasis (TMN staging). 11 But NPC, in contrast to other head and neck malignancies, is highly sensitive to radiation and chemotherapy. 12,13 High survival rates are reported for stage 1 and 2 diseases, but the prognosis for metastatic disease remains poor even with combined radiation and chemotherapy treatment, with disease relapse rates as high as 82%. 14,15 Unfortunately, the majority of NPC is diagnosed at an advanced stage because of non-specific presenting symptoms (cervical nodal enlargement, headache, nasal and aural dysfunction), delay in seeking treat...
Nasopharyngeal carcinoma (NPC) is a head and neck cancer rare throughout most of the world but common in certain geographic areas, such as southern Asia. While environmental factors and genetic susceptibility play important roles in NPC pathogenesis, the Epstein-Barr virus in particular has been implicated in the molecular abnormalities leading to NPC. There is upregulation of cellular proliferation pathways such as the Akt pathway, mitogen-activated protein kinases, and the Wnt pathway. Cell adhesion is compromised due to abnormal E-cadherin and β-catenin function. Aberrations in cell cycle are due to dysregulation of factors such as p16, cyclin D1, and cyclin E. Anti-apoptotic mechanisms are also upregulated. There are multiple abnormalities unique to NPC that are potential targets for novel treatments. Keywordsnasopharyngeal carcinoma (NPC); Epstein; Barr virus (EBV); LMP1; tumorigenesis; review Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma that usually develops around the ostium of the Eustachian tube in the lateral wall of the nasopharynx. 1 Though rare among whites, NPC is particularly common in the southern Chinese population of Guangdong, Inuits of Alaska, and native Greenlanders. 2,3 Chinese emigrants continue to have a high incidence of the disease, but the rate of NPC among ethnic Chinese born in North America is considerably lower than those born in China. 4 This epidemiologic evidence implies that both environmental factors and genetic susceptibility play roles in the development of NPC. The environmental factors may include exposure to nitrosamines in salted and pickled foods. 5 Certain human leukocyte antigen subtypes have been associated with NPC, as they have various genetic polymorphisms. 6 The World Health Organization classifies NPC based on histology. 7 Type 1, keratinizing squamous carcinoma, is characterized by well-differentiated cells that produce keratin. Type 2, nonkeratinizing squamous carcinoma, varies in cell differentiation but does not produce keratin. Type 3 is also nonkeratinizing, but is less differentiated, with highly variable cell types (clear cell, spindle cell, anaplastic). Types 2 and 3 NPC are Epstein-Barr virus (EBV) Correspondence to: D. M. Jablons, jablonsd@surgery.ucsf.edu. Standard treatment for NPC is radiotherapy, but concurrent adjuvant chemotherapy improves survival rates. 10 As with other cancers, the prognosis of NPC depends upon tumor size, lymph node involvement, and distant metastasis (TMN staging). 11 But NPC, in contrast to other head and neck malignancies, is highly sensitive to radiation and chemotherapy. 12,13 High survival rates are reported for stage 1 and 2 diseases, but the prognosis for metastatic disease remains poor even with combined radiation and chemotherapy treatment, with disease relapse rates as high as 82%. 14,15 Unfortunately, the majority of NPC is diagnosed at an advanced stage because of non-specific presenting symptoms (cervical nodal enlargement, headache, nasal and aural dysfunction), delay in seeking treat...
Hypoxia in solid tumors is common, which not only a major problem for radiation therapy but also leads to resistance to most anticancer drugs, importantly, appears to accelerate malignant progression and increase metastasis. We observed the change of the cell cycle and apoptosis in order to investigate effect of radiosensitivity induced by CoCl2 in esophageal cancer line Eca109 cells in vitro. Materials and methods Cell cultureEsophageal cancer line Eca109 cells, which was obtained from the Cancer Research Center of Forth Affiliated Hospital, Hebei Medical University, were cultured in RPMI1640 (Sigma, USA) supplemented with 10% FBS and penicillin/streptomycin (100 IU/50 μg/mL) in a humidified atmosphere containing 5% CO2 in air at 37 . Cells in exponential phase of growth were used to test. Hypoxia treatment induced by CoCl 2We studied the effect of increasing concentrations of CoCl2 (0, 50, 100, 150 and 200 μM) on Eca109 cells and observed a dose-dependent morphological change of the cells. Since 200 μM of CoCl2 appeared to be toxic for these cells, we chose the 150 μM concentration as hypoxia group and 0 μM as control group. Subgroup and irradiationAll Eca109 cells were divided into control, hypoxia, hypoxia plus irradiation and only irradiation groups. The cells were irradiated in ordinary temperature using 60 Co γ ray from therapeutic machine of dose rate 110 cGy/min with field area 20 × 20 cm and source-skin distance 80 cm. 0.5 cm tissue compensation was putted on culture flask. Cell cycle and apoptosis analysisCells cultured in control-oxygen, anerobic cultivation induced by CoCl2 for 8, 16, 24 h and irradiation groups were gathered and washed in ice-cold PBS before trypsinization, diluted to 1 × 10 5 /mL. After fixation with 75% ethanol, cells were digested with DNAse-free RNAse in PBS containing 50 mg/mL propidium iodide for DNAstaining. Cell cycle and apoptosis was detected by using Abstract Objective: To investigate the change of the cell cycle, apoptosis and radiosensitivity effect by CoCl2 induced hypoxia in esophageal cancer line Eca109 cells in vitro. Methods: The hypoxia culture model induced by 150 microM CoCl2 was established. The cell cycle and apoptosis were measured with flow cytometry (FCM). The radiosensitivity was analysized with clonogenic assay after irradiation alone or combined with hypoxia in Eca109 cells in vitro. Results: Eca109 cells were treated with 150 microM CoCl2 for 24 h, cell cycle arrest in G0/G1 phase increase and decreasing arrest in S phase with longer of hypoxiac time (0-24 h), the other rate of cell cycle and apoptosis did not change obviously. The G2/M phase block was arrested obviously in radiation alone comparing with the hypoxia plus irradiated group, apoptosis did not occur in Eca109 cell line following irradiation. The D0 value and cell surviving fraction of Eca109 cell was 2.48 Gy, 2.44 Gy and 97.33%, 96.33% in hypoxia and control group, respectively; the Dq value of Eca109 cell was 2.89 Gy, 0.52 Gy, the cell surviving fraction after radiation with 4 Gy was 48.3%...
Cell kinetic concepts have pervaded radiation therapy since the early part of the 20th century and have been instrumental in the development of modern radiotherapy. In this review, the fundamental radiobiological concepts that have been developed based on cell kinetic knowledge will be revisited and discussed in the context of contemporary radiation therapy. This will include how the proliferation characteristics, variation in sensitivity during the cell cycle and the extent of radiation-induced cell cycle delay translate into a variable time for the expression of damage, how cell kinetics interacts with hypoxia and how the response to fractionated radiation schedules is influenced by cell kinetics in terms of repair, redistribution, reoxygenation and repopulation. The promise of combining radiation with new biologically targeted agents and the potential of non-invasive positron emission tomography imaging of proliferation are areas where cell kinetics will continue to influence radiotherapy practice.
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