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NPC Patients (npc + patient)
Selected AbstractsOver-expression of phosphatase of regenerating liver-3 correlates with tumor progression and poor prognosis in nasopharyngeal carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 8 2009Jun Zhou Abstract This study aimed at clarifying the expression of phosphatase of regenerating liver-3 (PRL-3), one member of protein tyrosine phosphatase (PTP) superfamily, in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathologic features, including the survival of patients with NPC. Real-time PCR and Western blot showed that the expression level of PRL-3 was markedly higher in NPC cell lines than that in the normal nasopharyngeal epithelial cell at both mRNA and protein levels. Immunohistochemical analysis revealed overexpression of PRL-3 in 97 of 174 (55.7%) paraffin-embedded archival NPC biopsies. Statistical analysis showed that PRL-3 expression was positively correlated with N classification (p = 0.033), distant metastasis (M classification, p = 0.048) and clinical stage (p = 0.005) of patients. Patients with higher PRL-3 expression had shorter overall survival time, whereas patients with lower level of PRL-3 had better survival. Multivariate analysis suggested that PRL-3 expression might be an independent prognostic indicator for the survival of patients with NPC. Disruption of endogenous PRL-3 protein through a siRNA knockdown technique was shown to suppress the invasion ability and migration potency of 5-8F and HONE1 cells, substantially. Interestingly, we also found that no significant effect on the proliferation of 5-8F and HONE1 cells was observed after PRL-3 was down-regulated. Our results suggest that PRL-3 protein is a valuable marker for progression of NPC patients. High PRL-3 expression is associated with poor overall survival in patients with NPC. © 2008 Wiley-Liss, Inc. [source] Oxidative stress in NPC1 deficient cells: protective effect of allopregnanoloneJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9b 2009Stefania Zampieri Abstract Niemann-Pick C disease (NPC) is an autosomal recessive neurodegenerative disorder caused by the abnormal function of NPC1 or NPC2 proteins, leading to an accumulation of unesterified cholesterol and glycosphingolipids (GSLs) in the lysosomes. The mechanisms underlying the pathophysiology in NPC disease are not clear. Oxidative damage is implicated in the pathophysiology of different neurological disorders and the effect of GSL accumulation on the intracellular redox state has been documented. Therefore, we determined whether the intracellular redox state might contribute to the NPC disease pathophysiology. Because the treatment of NPC mice with allopregnanolone (ALLO) increases their lifespan and delays the onset of neurological impairment, we analysed the effect of ALLO on the oxidative damage in human NPC fibroblasts. Concentrations of reactive oxygen species (ROS) and lipid peroxidation were higher in fibroblasts from NPC patients than in fibroblasts from normal subjects. Fibroblasts from NPC patients were more susceptible to cell death through apoptosis after an acute oxidative insult. This process is mediated by activation of the NF-,B signalling pathway. Knockdown of NPC1 mRNA both in normal fibroblasts and in human SH-SY5Y neuroblastoma cells caused increased ROS concentrations. ALLO treatment of fibroblasts from NPC patients or NPC1 knockdown cells reduced the levels of ROS and lipid peroxidation and prevented peroxide-induced apoptosis and NF-kB activation. Thus, these findings suggest that oxidative stress might contribute to the NPC disease and ALLO might be beneficial in the treatment of the disease, at least in part, due to its ability to restore the intracellular redox state. [source] Raf kinase inhibitor protein correlates with sensitivity of nasopharyngeal carcinoma to radiotherapy,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2010Lin Ruan Abstract Raf kinase inhibitory protein (RKIP) is a metastasis suppressor whose expression is reduced in nasopharyngeal carcinoma (NPC) tissues and is absent in NPC metastases. To investigate the effect of RKIP on radiosensitivity of NPC, high metastatic 5-8F with low RKIP expression and non-metastatic 6-10B with high RKIP expression were stably transfected with plasmids that expressed sense and antisense RKIP cDNA. Overexpression of RKIP sensitized 5-8F cells to radiation-induced cell death, G2 -M cell cycle arrest and apoptosis. In contrast, downexpression of RKIP in 6-10B cells protected cells from radiation-induced cell death, G2 -M cell cycle arrest and apoptosis. In addition, RKIP expression altered the radiosensitivity of NPC cells through MEK and ERK phosphorylation changes of Raf-1/MEK/ERK signaling pathway. We further investigated the RKIP expression in NPC patients and its association with patients' survival after radiotherapy. Downexpression of RKIP was significantly correlated with advanced clinical stage, lymph node metastasis and radioresistance. Furthermore, survival curves showed that patients with RKIP downexpression had a poor prognosis and induced relapse. Multivariate analysis confirmed that RKIP expression was an independent prognostic indicator. The data suggested that RKIP was a potential biomarker for the radiosensitivity and prognosis of NPC, and its dysregulation might play an important role in the radioresistance of NPC. J. Cell. Biochem. 110: 975,984, 2010. © 2010 Wiley-Liss, Inc. [source] Comparison of three different serological techniques for primary diagnosis and monitoring of nasopharyngeal carcinoma in two age groups from TunisiaJOURNAL OF MEDICAL VIROLOGY, Issue 4 2005H. Karray Abstract Nasopharyngeal carcinoma (NPC) in Tunisia is characterized by its bimodal age distribution involving juvenile patients of 10,24 years and adult patients of 40,60 years. Three serological techniques were compared for primary diagnosis (N,=,117) and post-treatment monitoring (N,=,21) of NPC patients separated in two age groups. Immunofluorescence assay (IFA) was used as the "gold standard" for detection of IgG and IgA antibodies reactive with Epstein-Barr virus (EBV) early (EA) and viral capsid (VCA) antigens. Results were compared with ELISA measuring IgG and IgA antibody reactivity to defined EBNA1, EA, and VCA antigens. Immunoblot was used to reveal the molecular diversity underlying the anti-EBV IgG and IgA antibody responses. The results indicate that young NPC patients have significantly more restricted anti-EBV IgG and IgA antibody responses with aberrant IgG VCA/EA levels in 78% compared to 91.7% in elder patients. IgA VCA/EA was detected in 50% of young patients versus 89.4% for the elder group (P,<,0.001). Immunoblot revealed a reduced overall diversity of EBV antigen recognition for both IgG and IgA in young patients. A good concordance was observed between ELISA and IFA for primary NPC diagnosis with 81,91% overall agreement. Even better agreement (95,100%) was found for antibody changes during follow-up monitoring, showing declining reactivity in patients in remission and increasing reactivity in patients with persistent disease or relapse. ELISA for IgA anti-VCA-p18 and immunoblot proved most sensitive for predicting tumor relapse. VCA-p18 IgA ELISA seems suitable for routine diagnosis and early detection of NPC complication. J. Med. Virol. 75:593,602, 2005. © 2005 Wiley-Liss, Inc. [source] Human papillomavirus and WHO type I nasopharyngeal carcinoma,,THE LARYNGOSCOPE, Issue 10 2010Emily J. Lo BA Abstract Objectives: Nasopharyngeal carcinoma (NPC) is a rare cancer in the United States. An association between NPC and Epstein-Barr virus (EBV) is well-established for World Health Organization (WHO) types II and III (WHO-II/III) NPC but less well-established for WHO type I (WHO-I) NPC. Given the rise in oropharyngeal tumors positive for high-risk human papillomavirus (HPV) and the unique biology of WHO-I NPC, we examined the relationship between HPV and WHO-I NPC. Study Design: Retrospective case-comparison study. Methods: A search of a large multidisciplinary cancer center tumor registry identified 183 patients seen from January 1999 to December 2008 with incident NPC and no prior cancer. Available paraffin-embedded tumor specimens (N = 30) were analyzed for oncogenic HPV status by in situ hybridization (ISH) and polymerase chain reaction (PCR) for HPV-16 and HPV-18; EBV status by ISH; and p16 expression by immunohistochemistry. Demographic parameters, including race and smoking, were obtained from the medical records. Results: Among the 18 WHO-I NPC patients, 66% (N = 12) were smokers and 17% (N = 3) Asian; among the 165 WHO-II/III NPC patients, 44% (N = 73) were smokers and 24% (N = 39) Asian. Eight WHO-I NPC patients had available paraffin blocks; five of six were HPV-16-positive by PCR and four of eight were HPV-positive by ISH; only two of eight (25%) were EBV-positive. Twenty-two WHO-II/III NPC patients had available paraffin blocks; only 1 was HPV-positive by ISH, and 13 of 22 (60%) were EBV-positive. Conclusions: These results suggest that WHO-I NPC is associated with oncogenic HPV, although larger studies are needed to verify these findings. Laryngoscope, 2010 [source] Malignancies of the Ear in Irradiated Patients of Nasopharyngeal CarcinomaTHE LARYNGOSCOPE, Issue 12 2008Wu-Chia Lo MD Abstract Objectives/Hypothesis: To report on the clinical profiles and treatment experiences of patients with second primary ear malignancy after treatment of nasopharyngeal carcinoma (NPC). Study Design: Retrospective case series. Methods: A retrospective review of the clinical outcomes and pathology of 11 irradiated NPC patients who subsequently had second primary malignancies of the ear at a single institution. Results: Ten tumors were squamous cell carcinoma and one tumor was chondrosarcoma occurring within the radiation field of previous treatment for NPC. The interval between previous radiotherapy and diagnosis of ear malignancy was 3 to 27 years with a median time of 17 years. Six tumors were located in the external auditory canal, two in the middle ear cavity, two in the periauricular region and one in the mastoid cavity. Four patients underwent surgery, and the other seven patients underwent surgery plus adjuvant radiotherapy. The 3-year disease-free and overall survival rates were 30.3% and 20%, respectively. Conclusions: Postirradiated malignancy of the ear is extremely rare, but is one of the causes of death for NPC long-term survivors despite curative-intended treatment with surgery plus adjuvant radiotherapy is instituted. [source] Pretherapy quantitative measurement of circulating Epstein,Barr virus DNA is predictive of posttherapy distant failure in patients with early-stage nasopharyngeal carcinoma of undifferentiated typeCANCER, Issue 2 2003Sing-fai Leung M.D. Abstract BACKGROUND Patients with International Union Against Cancer (UICC) Stage I,II nasopharyngeal carcinoma (NPC) appear to have a relatively favorable prognosis and generally are excluded from trials of combined modality treatment. More recently, plasma/serum cell-free Epstein-Barr virus (EBV) DNA has been shown to be measurable in the majority of NPC patients at the time of diagnosis, and appears to have prognostic significance. However, within Stage I-II disease, in which failure events are infrequent, the prognostic impact of the pretreatment EBV DNA level has not been addressed to our knowledge. This issue has management implications because different therapeutic strategies currently are employed for patients with good-risk and those with poor-risk NPC. METHODS A cohort of 90 patients with UICC Stage I-II NPC (World Health Organization Grade 2/3 histology) had their pretherapy plasma/serum EBV DNA levels determined by a quantitative polymerase chain reaction assay and correlated with the probability of posttherapy failure. All patients received radiation therapy only, except for three patients who also received concurrent chemotherapy. Kaplan,Meier plots of the probability of locoregional failure, distant failure, and cancer-specific survival were compared with reference to clinical stage and EBV DNA levels. RESULTS With a median follow-up time of 45 months, 12 patients and 7 patients, respectively, had developed locoregional and distant failures, including 2 patients with both local and distant failures. Patients with distant failure had significantly higher pretherapy EBV DNA levels than those without failure (a median of 13,219 copies/mL [interquatile-range, 274,635 copies/mL] vs. a median of 423 copies/mL [interquatile-range, 2753 copies/mL]). The probability of distant failure was significantly higher in patients with high (> 4000 copies/mL plasma) compared with low EBV DNA levels (P = 0.0001, log-rank test) and for Stage IIB disease compared with Stage I and Stage IIA disease combined (P = 0.0149, log-rank test), but was not significantly different between patients with Stage II and those with Stage I disease. The risks of locoregional failure were not significantly different between patients with high and those with low EBV DNA levels, and also was not significantly different between clinical substages. Approximately 35% of patients with Stage IIB disease were in the at-risk group for distant failure, as identified by high EBV DNA levels. CONCLUSIONS Within a group of patients with UICC Stage I-II NPC, the pretherapy plasma EBV DNA level was found to identify a poor-risk group with a probability of distant failure similar to that of patients with advanced stage disease. This group of patients may warrant management considerations currently applicable only to cases of Stage III-IV disease. The prognostic significance of designating Stage IIB disease as per the 1997 UICC staging was confirmed, although the pretherapy EBV DNA level appears to be a more powerful prognostic discriminator in patients with early-stage NPC. Cancer 2003;98:288,91. © 2003 American Cancer Society. DOI 10.1002/cncr.11496 [source] Identification of 25 new mutations in 40 unrelated Spanish Niemann-Pick type C patients: genotype-phenotype correlationsCLINICAL GENETICS, Issue 3 2005EM Fernandez-Valero To better characterize Niemann-Pick type C (NPC) in Spain and improve genetic counselling, molecular analyses were carried out in 40 unrelated Spanish patients. The search identified 70/80 alleles (88%) involving 38 different NPC1 mutations, 26 of which are described for the first time. No patient with NPC2 mutations was identified. The novel NPC1 mutations include 14 amino acid substitutions [R372W (c.1114C > T), P434L (c.1301C > T), C479Y (c.1436G > A), K576R (c.1727G > A), V727F (c.2179G > T), M754K (c.2261T > A), S865L (c.2594C > T), A926T (c.2776G > A), D948H (c.2842G > C), V959E (c.2876T > A), T1036K (c.3107C > A), T1066N (c.3197C > A), N1156I (c.3467A > T) and F1224L (c.3672C > G)], four stop codon [W260X (c.780G > A), S425X (c.1274C > A), C645X (c.1935T > A) and R1059X (c.3175C > T)], two donor splice-site mutations [IVS7+1G > A (g.31432G > A) and IVS21+2insG (g.51871insG)], one in-frame mutation [N961_F966delinsS (c.2882del16bpins1bp)] and five frameshift mutations [V299fsX8 (c.895insT), A558fsX11 (c.1673insG), C778fsX10 (c.2334insT), G993fsX3 (c.2973_78delG) and F1221fsX20 (c.3662delT)]. We also identified three novel changes [V562V (c.1686G > A), A580A (c.1740C > G) and A1187A (c.3561G > T)] in three independent NPC patients and five polymorphisms that have been described previously. The combination of these polymorphisms gave rise to the establishment of different haplotypes. Linkage disequilibrium was detected between mutations C177Y and G993fsX3 and specific haplotypes, suggesting a unique origin for these mutations. In contrast, I1061T mutation showed at least two different origins. The most prevalent mutations in Spanish patients were I1061T, Q775P, C177Y and P1007A (10, 7, 7 and 5% of alleles, respectively). Our data in homozygous patients indicate that the Q775P mutation correlates with a severe infantile neurological form and the C177Y mutation with a late infantile clinical phenotype. [source] | |||||||||||||