Isotropic volumetric MRI for displaying cranial perineural spread of cranial nerve in nasopharyngeal carcinoma

Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal carcinoma were prospectively enrolled.MR scanning,including three-dimensional liver acquisition with volume acceleration-flexible(3D LAVA_Flex)image,T2WI with fat suppression(T2WI-FS),T1WI,contrast enhancement(CE)T1WI-FS of nasopharynx and neck region were performed.The displaying rates of CN PNS were evaluated and compared between 3D LAVA_Flex and T2WI-FS,T1WI,CE-T1WI-FS at patient level,CN group level and neural level,respectively.Results The displaying rate of CN PNS in all 87 nasopharyngeal carcinoma patients by 3D LAVA_Flex sequence was 49.43%(43/87),higher than that of conventional MRI(30/87,34.48%,P=0.001).Among 59 patients with advanced nasopharyngeal carcinoma diagnosed with conventional sequences,the displaying rate of CN PNS was 71.19%(42/59)by 3D LAVA-Flex sequence,higher than that of conventional MRI(30/59,50.85%,P=0.001).At both patient level and posterior CN level,significant differences of the displaying rate of CN PNS were found between 3D LAVA-Flex sequence and T2WI-FS,T1WI,CE-T1WI-FS,while at CN level,the displaying rates of mandibular nerve PNS,CNⅨ—ⅪPNS in jugular foramen(P<0.05)and CNⅨ—ⅫPNS in carotid space of 3D LAVA_Flex sequence were all significantly higher than that of T2WI-FS,T1WI and CE-T1WI-FS(all P<0.05),of PNS of CNⅢ—Ⅴin cavernous sinus were higher than that of T2WI-FS(P<0.05),while of PNS of hypoglossal nerve were significantly higher than that of T2WI-FS and T1WI(both P<0.05).Conclusion 3D LAVA_Flex sequence could be used to effectively display CN PNS of nasopharyngeal carcinoma.

Signal intensity changes of dentate nucleus on plain MR T1WI innasopharyngeal carcinoma patients after radiotherapy andmultiple injections of gadolinium-base contrast agent

Objective To observe changes of plain MR T1WI signal intensity of dentate nucleus in nasopharyngeal carcinoma patients after radiotherapy and multiple times of intravenous injection of gadolinium-based contrast agent(GBCA).Methods Fifty patients with pathologically confirmed nasopharyngeal carcinoma and received intensity-modulated radiotherapy were retrospectively enrolled as the nasopharyngeal carcinoma group,and 50 patients with other malignant tumors and without history of brain radiotherapy were retrospectively enrolled as the control group.All patients received yearly GBCA enhanced MR examinations for the nasopharynx or the head.T1WI signal intensities of the dentate nucleus and the pons on same plane were measured based on images in the year of confirmed diagnosis(recorded as the first year)and in the second to the fifth years.T1WI signal intensity ratio of year i(ranging from 1 to 5)was calculated with values of dentate nucleus divided by values of the pons(ΔSI i),while the percentage of relative changes of year j(ranging from 2 to 5)was calculated withΔSI j compared toΔSI 1(Rchange j).The values of these two parameters were compared,and the correlation ofΔSI and GBCA injection year-time was evaluated within each group.Results No significant difference of gender,age norΔSI 1 was found between groups(all P>0.05).The second to the fifth yearΔSI and Rchange in nasopharyngeal carcinoma group were all higher than those in control group(all P<0.05).Within both groups,ΔSI was positively correlated with GBCA injection year-time(both P<0.05).Conclusion Patients with nasopharyngeal carcinoma who underwent radiotherapy and multiple times of intravenous injection of GBCA tended to be found with gradually worsening GBCA deposition in dentate nucleus,for which radiotherapy might be a risk factor.

Pretreatment platelet count improves the prognostic performance of the TNM staging system and aids in planning therapeutic regimens for nasopharyngeal carcinoma:a singleinstitutional study of 2,626 patients

Introduction:Thrombocytosis has been identified as an unfavorable prognostic factor in several types of cancer.This study aimed to evaluate the prognostic value of pretreatment platelet count in association with the TNM staging system and therapeutic regimens in patients with nasopharyngeal carcinoma(NPC).Methods:A total of 2,626 patients with NPC were retrospectively analyzed.Platelet count >300 × 10~9/L was defined as thrombocytosis.Matched-pair analysis was performed between patients receiving chemoradiotherapy and radiotherapy.Results:Multivariate analysis showed that platelet count was an independent unfavorable prognostic factor for overall survival(OS)[hazard ratio(HR) = 1.810,95%confidence interval(CI) = 1.531-2.140,P < 0.001]and distant metastasis-free survival(DMFS)(HR = 1.873,95%CI = 1.475-2.379,P < 0.001) in the entire patient cohort.Further subgroup analysis revealed that increased platelet count was an independent unfavorable prognostic factor for OS and DMFS in patients with NPC stratified by early and advanced T category,N category,or TNM classification(all P < 0.001).Receiver operating characteristic(ROC) curves verified that the predictive value of TNM classification for OS was improved when combined with pretreatment platelet count(P = 0.030).Matched-pair analysis showed that chemoradiotherapy significantly improved OS only in advanced-stage NPC with thrombocytosis(HR = 0.416,95%CI = 0.226-0.765,P = 0.005).Conclusions:Pretreatment platelet count,when combined with TNM classification,is a useful indicator for metastasis and survival in patients with NPC.It may improve the predictive value of the TNM classification and help to identify patients likely to benefit from more aggressive therapeutic regimens.

Relationship between traditional Chinese medicine syndrome differentiation and imaging characterization to the radiosensitivity of nasopharyngeal carcinoma

Background and Objective: Traditional Chinese medicine (TCM) is a well established and time-honored practice in China, employing syndrome differentiation as a basis for the treatment of disease. According to different TCM syndrome typing findings, combining modern medical methods with TCM approaches can improve the quality of life and comprehensive effect on patients with nasopharyngeal carcinoma (NPC). This study investigated the relationship between TCM syndrome typing and imaging characterization to radiosensitivity as to provide objective evidence for the integration of Chinese and modern medical approaches in the treatment of NPC. Methods: Prior to treatment, TCM syndrome typing, computed tomography (CT) and magnetic resonance imaging (MRI) were performed on 147 patients pathologically classified with NPC. The status of tumor remission was radiologically evaluated at accumulated doses of 20 Gy, 40 Gy and 60 Gy, and at 3 months after completion of radiotherapy. Statistical results were analyzed by the Friedman and K-W test procedures. Results: Prior to treatment, TCM syndrome typing of NPC included Lung Heat, Blood Stasis, Phlegm Congealment and Blood Stasis-Phlegm Congealment. Lung Heat typing accounted for the highest proportion at 34.7% (51/147), followed by Phlegm Congealment at 32.7% (48/147), Blood Stasis at 17.0% (25/147) and Blood Stasis-Phlegm Congealment at 15.7% (23/147). Radiological imaging demonstrated a higher incidence of cervical lymph node metastases in Phlegm Congealment and Blood Stasis-Phlegm Congealment types (P < 0.05), while Blood Stasis and Blood Stasis-Phlegm Congealment types were more prone to skull base invasion (P < 0.05). Residual tumor size was larger in Blood Stasis and Blood Stasis-Phlegm Congealment types than in Lung Heat and Phlegm Congealment types after 3 months of treatment (P < 0.05). Conclusions: Different radiological manifestations were observed in TCM syndrome typed NPC patients, with lesser radiosensitivity demonstrated in the Blood Stasis and the Blood Stasis-Phlegm Congealment types relative to the Lung Heat and Phlegm Congealment types.

The Comparison of Diagnostic Significance of Narrow Band Imaging in Contrast of White Light Endoscopy in the Assessment of Nasopharyngeal Cancer

Background: Narrow band imaging (NBI) is reported to improve the diagnostic importance of nasopharyngeal cancer. The purpose of this review was to evaluate the diagnostic significance of NBI in the literature and compare it to the conventional white light endoscopy. The use of narrow band imaging (NBI) and further technological achievements concerning the resolution and magnification of endoscopic images have in the past 15 years. With the use of NBI, superficial mucosal lesions, which may be missed by standard WLI endoscopy, can be identified easily by their neoangiogenic pattern. Objective:?To assess diagnostic value of the narrow band imaging and white light endoscopy in nasopharyngeal carcinoma and compare diagnostic values (sensitivity, specificity, positive predictive value and negative predictive value) with white light endoscopy. Search Methods: From 2010 to 2020, data was searched from electronic databases such as PubMed, web of science. We used narrow band imaging as a key word accordance with diagnostic modalities such as sensitivity, specificity, PPV and NPV and data were collected. Results: We have found mainly 6 studies have discussed about diagnostic value of endoscopy in nasopharyngeal carcinoma in the total of 2746 suspected patients. Among them, 5 studies have compared diagnostic values such as sensitivity, specificity, positive predictive value and negative predictive value between NBI and WLE. Among 5 studies, 4 studies have found higher sensitivity in NBI, 2 studies found higher 1 equal to WLE specificity in NBI. 3 studies have compared PPV and NPV between NBI and WLE. Among them, all the studies found higher PPV and NPV in NBI than WLE. Conclusion: Recently?developed narrow band imaging has a great significance in the diagnosis of nasopharyngeal carcinoma. Although NBI has also encountered some problem such as contact bleeding and darker image. So, further evaluation should be done.

THREE-DIMENSIONAL CONFORMAL RADIATION THERAPY FOR LOCALLY RECURRENT NASOPHARYNGEAL CARCINOMA

Objective: To investigate the safety and effectiveness of three-dimensional conformal radiation therapy (3-D CRT) for locally recurrent nasopharyngeal carcinoma (NPC). Methods: From April 1998 to March 2000, 34 patients who had undergone previous external beam radiation therapy were retreated with 3-D CRT for locally recurrent NPC (33 poorly differentiated squamous cell carcinomas, 1 adenoma). The patients were re-staged according to Huaqing staging system with the following distribution: T1N0M0 in 5 cases, T2N0M0 in 11 cases, T3N0M0 in 12 cases, T4N0M0 in 6 cases. The maximal dimension of the gross tumor volume (GTV) ranged from 1.0 cm to 5.0 cm (median: 2.9 cm). CT simulation and 3-D planning were used to ensure full and conformal coverage of the planning target volume (PTV) by treated volume, while minimizing the absorbed dose of the adjacent normal tissue. 5–7 static conformal coplanar or noncoplanar portals were delivered for each fraction irradiation. The total dose delivered ranged from 65–70 Gy, with 2.5 Gy per fractionation, one fractionation per day, 5 days a week. Median follow-up time from 3-D CRT was 25 months (range: 12–36 months). Results: Over the follow-up period, local recurrence was observed in 3 patients, regional failure in 3, distant metastasis in 3, and six patients died; 88.2% (30/34) of the patient maintained local control, 82.4% (28/34) survived, and 76.5% (26/34) survived with no evidence of tumor. Acute complications were minor and few. The overall incidence of late complication was 20.6% (7/34), and severe complication was 14.7% (5/34), after re-irradiation with 3-D CRT. Conclusion: 3-D CRT is safety and effectiveness for most of the patients with locally recurrent NPC. Our preliminary results indicate a high local control rate and a low complication rate. The long-term curative effect and sequelae await further study.

Magnetic resonance imaging in diagnosis of radiation encephalopathy after radiotherapy for nasopharyngeal carcinoma

Radiation encephalopathy(REP) after radiotherapy was investigated by magnetic resonance imaging (MRI) in 84 patients with nasopharyngeal carcinoma(NC). The lesions were found mainly in the bilateral temporal lobes, brain stems and cerebella. In T1-weighte

A PROPOPSAL CONCERNING THE HISTOLOGICAL TYPING OF PRIMARY NASOPHARYNGEAL CARCINOMA

A proposal concerning the histological typing of primary nasopharyngeal carcinoma is offered in order to coincide with pathologic terms used both by Chinese and foreign pathologists and reflect the achievements in the research field of NPC. This proposal was worked out mainly basing upon the authors’ diagnostic experience gained in the past 30 years and the international criteria for tumor classification. Primary nasopharyngeal carcinoma could be classified into four major types, namely, keratinizing squamous cell carcinoma (KSCC), non- keratinizing carcinoma (NKC), adenocarcinoma (AC) and carcinomain-situ (CIS). KSCC could be graded as being well, moderately and poorly differentiated according to the amount of keratinization and intercellular bridges presented in the biopsy slide. The NKC is the most frequent type seen in the high-incidence area of NPC, and could also be subdivided into differentiated and undifferentiated variants. Actually, three grades of KSCC and two variants of NKC are a reflection of different degrees of squamous differentiation. They are consistently associated with Epstein-Barr virus (EBV) infection. There are two major categories of nasopharyngeal AC, namely, traditional and salivary-gland type. As contrasted with KSCC and NKC, nasopharyngeal AC is rarely infected with EBV. There are two subtypes of CIS, namely, squamous- and columnar-cell type. The histological typing concerning the primary nasopharyngeal carcinoma offered above is really a practical proposal and also coincided with the international usage. This proposal can be mastered easily and the authors recommend its routine use in diagnostic pathology.

Technical and Dosimetric Study of Four Facio-cervical Fields Conformal Radiotherapy for Nasopharyngeal Carcinoma

Objective： The aim of this study is to establish the methods of four facio-cervical fields＇ conformal radiotherapy （4F-CRT） for nasopharyngeal carcinoma （NPC）, and to optimize the methods for clinical practice. Methods and Materials： 40 patients with untreated NPC of T1-T4 （1997AJCC Staging System） were rolled into this study. Conventional and four ratio-cervical fields conform plans were designed for each patient using Pinnacle 8.0 three-dimension treatment planning system （3D-TPS）： 1） Improved plan, four ratio-cervical fields＇conform plans, anterior, posterior ratio-cervical and 2 lateral opposing facio-eervical fields; 2） Conventional plan, two lateral opposing facio-cervical fields only with the same dose delivered to the target in each plan, close volume histograms （DVHs） of the targets and normal organs, brain stem, spinal cord, parotid glands, and temporal mandibular joints （TMJs） were compared and the dose distribution were evaluated. Results： 1） The dose distribution of the improved plan could meet the requirements for the target volume. 2） There was not any significant difference in the dose of spinal cord between the two plans. The mean doses of Dmax for brain stem in conventional plan were much lower than those in the improved plan, though both were within safety limits. 3） Compared with the conventional plans, the improved plan significantly decreased the hotspot areas in the target volume and had better parotid glands and temporal mandibular joints sparing effect. Conclusion： Compared with the conventional plan, the improved plan provides satisfactory dose coverage to the tumor volume and better sparing of the parotid gland, TMJs and other normal tissues in external beam radiotherapy of NPC.

Expression of Cyclooxygenase-2 in Nasopharyngeal Carcinoma and Its Relation to Angiogenesis and Prognosis

Objective： The purpose of this study was to evaluate cyclooxygenase-2 （COX-2） expression in nasopharyngeal carcinoma （NPC） and its correlation with clinicopathologic features, angiogenesis, and prognosis. Methods： The expressions of COX-2 and vascular endothelial growth factor （VEGF） and microvascular density （MVD） were determined with immunohistochemical methods in eighty-six NPC patients followed up over 5 years. Results： Sixty-three tumors （73.3%） were classified as COX-2 positive. COX-2 expression was positively related to VEGF expression （r=0.438, P〈0.01） and correlated with the tumor pathological grade, extent of primary lesion, lymph node metastasis, distant metastasis and shorter survival. Conclusion： Our results suggest that COX-2, being highly expressed and strongly correlated with angiogenesis in nasopharyngeal carcinoma, is apt to be used as a predictor of prognosis, including local recurrence and distant metastasis.

基于IMRT同步放化疗方案治疗局部晚期鼻咽癌不良预后危险因素及预测模型构建

目的探讨基于调强放疗(IMRT)同步放化疗方案治疗局部晚期鼻咽癌不良预后危险因素并构建预测模型,为临床诊疗方案优化及预后改善提供更多参考。方法收集2012年1月~2017年12月梅州市人民医院接受基于IMRT同步放化疗方案治疗局部晚期鼻咽癌患者190例,分析临床特征资料和随访生存情况,采用单因素和多因素评价患者不良预后独立危险因素;基于独立危险因素构建列线图模型并评价模型预后预测效能。结果190例患者随访过程中死亡26例,累积1年、3年及5年总生存率分别为97.4%、90.7%、87.0%。单因素分析结果显示,年龄、淋巴细胞与单核细胞绝对值比值、乳酸脱氢酶、颅底侵犯、N分级及辅助化疗情况均与局部晚期鼻咽癌不良预后有关,差异有统计学意义(P<0.05)。多因素分析结果显示,乳酸脱氢酶水平≥185 IU/L、颅底侵犯及N3均是局部晚期鼻咽癌不良预后独立危险因素(P<0.05)。将多因素分析有统计学意义指标纳入局部晚期鼻咽癌患者总生存时间列线图模型,患者总生存时间列线图模型用于累积1年、3年及5年总生存时间C-index为0.84(95%CI:0.72~0.86),总生存时间预测AUC分别为0.87(95%CI:0.75~0.93)、0.90(95%CI:0.79~0.96)、0.85(95%CI:0.80~0.98)。结论接受基于IMRT同步放化疗方案治疗局部晚期鼻咽癌患者不良预后可能与乳酸脱氢酶水平、有无颅底侵犯及N分级等密切相关,而根据上述预后因素构建线列图模型在预测患者随访总生存时间方面具有良好效能。

Epigenetic disruption of cell signaling in nasopharyngeal carcinoma

Nasopharyngeal carcinoma(NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia.Alternative to genetic changes,aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/or histone modifications.These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC.In this review,we summarize the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research.Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.

Is nasopharyngeal cancer really a “Cantonese cancer”?

Nasopharyngeal cancer(NPC) is endemic in Southern China,with Guandong province and Hong Kong reporting some of the highest incidences in the world.The journal Science has called it a "Cantonese cancer".We propose that in fact NPC is a cancer that originated in the Bai-Yue("proto-Tai-Kadai" or "proto-Austronesian" or "proto-Zhuang") peoples and was transmitted to the Han Chinese in southern China through intermarriage.However,the work by John Ho raised the profile of NPC,and because of the high incidence of NPC in Hong Kong and Guangzhou,NPC became known as a Cantonese cancer.We searched historical articles,articles cited in PubMed,Google,monographs,books and Internet articles relating to genetics of the peoples with high populations of NPC.The migration history of these various peoples was extensively researched,and where possible,their genetic fingerprint identified to corroborate with historical accounts.Genetic and anthropological evidence suggest there are a lot of similarities between the Bai-Yue and the aboriginal peoples of Borneo and Northeast India;between Inuit of Greenland,Austronesian Mayalo-Polynesians of Southeast Asia and Polynesians of Oceania,suggesting some common ancestry.Genetic studies also suggest the present Cantonese,Minnans and Hakkas are probably an admixture of northern Han and southern Bai-Yue.All these populations have a high incidence of NPC.Very early contact between southern Chinese and peoples of East Africa and Arabia can also account for the intermediate incidence of NPC in these regions.

The results and prognosis of different treatment modalities for solitary metastatic lung tumor from nasopharyngeal carcinoma:a retrospective study of 105 cases

Background and Objective:Nasopharyngeal carcinoma (NPC) is known for its propensity for distant metastases.Lung metastasis is one of the most important causes of death for patients with NPC.Solitary metastatic lung tumor from NPC is a distinctive group associated with a better survival.This study was to find a more effective treatment modality and prognostic factors for the group.Methods:Clinical data of 105 cases of solitary metastatic lung tumor from NPC were retrospectively analyzed.Survival rate was calculated by the Kaplan-Meier method.The difference of survival between the patients treated by different modalities was evaluated by the log-rank test.The Cox univariate and multivariate analyses of gender, age, pathologic type, stage, adjuvant chemotherapy, evaluation of treatment for NPC, disease-free interval, size of metastatic tumor, pulmonary hilar and/or mediastinal lymph node metastasis, treatment modalities, recurrent distant metastases and/or relapse of NPC were conducted.Results:The local control rate was 53.8% in chemotherapy group, 88.0% in radiotherapy +/-chemotherapy group, and 96.4% in operation +/-chemotherapy group (P<0.01).The most promising progression-free survival (PFS) and overall survival (OS) were obtained with operation +/-chemotherapy and followed by radiotherapy +/-chemotherapy.Both of them showed much better efficacy than chemotherapy (P<0.001).The Cox multivariate analysis showed that recurrent distant metastases and/or relapse of NPC affected the survival (OR=2.087, 95% CI=1.277-3.410, P=0.003).The T stage of NPC, size of metastatic tumor, hilar and/or mediastinal lymph node metastasis, and the treatment modality were independent prognostic factors.Conclusions:Operation +/-chemotherapy and radiotherapy +/-chemotherapy are better treatment of solitary metastatic lung tumor from NPC, which could improve the local control and prolong the PFS and OS.Chemotherapy is recommended for patients with higher T stage of NPC, size of metastatic tumor ≥3 cm, pulmonary hilar and/or mediastinal lymph node metastasis.

Effect of heparin on apoptosis in human nasopharyngeal carcinoma CNE2 cells

In order to study the mechanism of the effect of heparin on apoptosis in carcinoma cells, the nasopharyngeal carcinoma cell line CNE2 was used to identify the effect of heparin on apoptosis associated with the expression of c-myc, bax, bcl-2 proteins by use of Hoechst 33258 staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), agarose gel electrophoresis, and flow cytometry, as well as Western blot analysis. The results showed that heparin induced apoptosis of CNE2 cells including the morphologic changes such as reduction in the volume, and the nuclear chromatin condensation, as well as the 'ladder pattern' revealed by agarose gel electrophoresis of DNA in a concentration-dependent manner. The number of TUNEL-positive cells was dramatically increased to 33.6+/-1.2% from 2.8+/-0.3% by treatment with heparin in different concentrations (10 to approximately 40 kU/L). The apoptotic index was increased to 32.5% from 3.5% by detecting SubG1 peaks on flow cytometry. Western blot analysis showed that levels of bcl-2, bax and c-myc were significantly overexpressed by treatment with the increase of heparin concentrations. These results suggest that heparin induces apoptosis of CNE2 cells, which may be regulated by differential expression of apoptosis-related genes.

CT-guided needle biopsy through mandibular area for the diagnosis of nasopharyngeal carcinoma in the parapharyngeal space

Background and Objective: The primary submucous type of nasopharyngeal carcinoma (NPC) or the recurrent NPC in the parapharyngeal space is difficult to be diagnosed histologically by conventional biopsy because of the obstruction of the surrounding structures. This study was performed to evaluate the needle biopsy approach through the madibular area into the parapharyngeal space under the guidance of computed tomography (CT) for NPC. Methods: Between July 6, 2005 and October 23, 2009, a total of 6 patients were enrolled into the study. Two patients with cervical lymph node metastasis were clinically suspicious of NPC according to their clinical manifestations. However, no cancer cell could be found by repeated nasopharyngeal biopsies followed by histologic examinations. The other 4 patients were diagnosed with recurrent NPCs by magnetic resonance imaging (MRI) or/and positron emission tomography (PET)-CT scan, showing tumors in the parapharyngeal spaces in 3 patients and enlarged retropharyngeal lymph node in 1 patient. The CT-guided puncture was performed through the mandibular skin and the cutting needle biopsy was taken at the parapharyngeal space focus. Results: All the cutting needle biopsies of projected locations have been performed safely. Finally, all the 7 specimens met the requirement of pathologic diagnosis and the cases were all confirmed histologically to be NPCs. The main complication was mild ache at the puncture point. No blood vessel or nerve was injured and no patient needed special treatment. Conclusions: The CT-guided puncture biopsy of the parapharyngeal space through the mandibular area is simple and feasible. It can be an additional option for routine nasopharyngeal biopsy.

Nasopharyngeal carcinoma in the Northeastern states of India

Nasopharyngeal cancer (NPC) is a rare disease in most parts of the world, except for Southeast Asia, some parts of North Africa and the Arctic. It is mostly seen in people of Chinese origin. In India, NPC is also rare, except for the Hill States of Northeast India, particularly Nagaland, Manipur, and Mizoram. The striking feature of NPC in Northeast India is that the incidence ranges over the complete spectrum from the lowest (as 0.5/100 000 to 2.0/100 000 among Caucasoid) to the highest (as ~20/100 000 among Cantonese/Zhongshan dialect Chinese). The age-adjusted rate of NPC in Kohima district of Nagaland State is 19.4/100 000, which is among the highest recorded rates. By contrast, in Assam, one of the so-called Hill States but not itself a hilly state, NPC is much less common. The Northeastern region is distinguished by a preponderance of the Tibeto-Burman languages and by variable mongoloid features among peoples of the region. The nature of the migratory populations who are presumed to be bearers of the mongoloid risk is unknown, but these NPC occurrence features provide an outstanding opportunity for NPC risk investigation, such as that of the hypothesis of Wee et al. for westward displacement of Chinese aborigines following the last glacial maximum.

On the trails of markers and proxies:the socio-cognitive technologies of human movement,knowledge assemblage,and their relevance to the etiology of nasopharyngeal carcinoma

Bacteria,pigs,rats,pots,plants,words,bones,stones,earrings,diseases,and genetic indicators of all varieties are markers and proxies for the complexity of interweaving trails and stories integral to understanding human movement and knowledge assemblage in Southeast Asia and around the world.Understanding human movement and knowledge assemblage is central to comprehending the genetic basis of disease,especially of a cancer like nasopharyngeal carcinoma.The problem is that the markers and trails,taken in isolation,do not all tell the same story.Human movement and knowledge assemblage are in constant interaction in an adaptive process of co-production with genes,terrain,climate,sea level changes,kinship relations,diet,materials,food and transport technologies,social and cognitive technologies,and knowledge strategies and transmission.Nasopharyngeal carcinoma is the outcome of an adaptive process involving physical,social,and genetic components.

Correlation of Skp2 overexpression to prognosis of patients with nasopharyngeal carcinoma from South China

S-phase kinase-associated protein 2 (Skp2), which plays a role in cell cycle regulation, is commonly overexpressed in a variety of human cancers and associated with poor prognosis. However, its role in nasopharyngeal carcinoma (NPC) is not well understood. In this study, we examined the clinical significance of Skp2, with a particular emphasis on overall survival (OS) and disease-free survival (DFS), in NPC cases in South China, where NPC is an epidemic. Additionally, we explored the function of Skp2 in maintaining a cancer stem cell -like phenotype in NPC cell lines. Skp2 expression was assessed for 127 NPC patients using tissue microarrays and immunohistochemistry and analyzed together with clinicopathologic features, OS, and DFS. Skp2 expression was detectable, or positive, in 75.6% of patients. Although there was no correlation between Skp2 and any clinicopathologic factor, Skp2 expression significantly portended inferior OS (P = 0.013) and DFS (P = 0.012). In the multivariate model, Skp2 expression remained significantly predictive of poor OS [P = 0.009, risk ratio (RR) = 4.06] and DFS (P = 0.008, RR = 3.56), and this was also true for clinical stage (P = 0.012 and RR=3.201 for OS; P = 0.002 and RR=1.94 for DFS) and sex (P = 0.016 and RR=0.31 for OS; P = 0.006 and RR = 0.27 for DFS). After Skp2 knockdown, a colony formation assay was used to evaluate the self-renewal property of stem-like cells in the NPC cell lines CNE-1 and CNE-2. The colony formation efficiency in CNE-1 and CNE-2 cells was decreased. In Skp2-transfected CNE-1 and CNE-2 cells, side population (SP) proportion was increased as detected by flow cytometry. Skp2 is an independent prognostic marker for OS and DFS in NPC. Skp2 may play a role in maintaining the cancer stem cell-like phenotype of NPC cell lines.

Detection of nasopharyngeal carcinoma using surface-enhanced laser desorption and ionization mass spectrometry profiles of the serum proteome

Background and Objective: Early diagnosis of nasopharyngeal carcinoma (NPC) is difficult due to the insufficient specificity of the conventional examination method. This study was to investigate potential and consistent biomarkers for NPC, particularly for early detection of NPC. Methods: A proteomic pattern was identified in a training set (134 NPC patients and 73 control individuals) using the surface-enhanced laser desorption and ionization-mass spectrometry (SELDI-MS), and used to screen the test set (44 NPC patients and 25 control individuals) to determine the screening accuracy. To confirm the accuracy, it was used to test another group of 52 NPC patients and 32 healthy individuals at 6 months later. Results: Eight proteomic biomarkers with top-scored peak mass/charge ratios (m/z) of 8605 Da, 5320 Da, 5355 Da, 5380 Da, 5336 Da, 2791 Da, 7154 Da, and 9366 Da were selected as the potential biomarkers of NPC with a sensitivity of 90.9% (40/44) and a specificity of 92.0% (23/25). The performance was better than the current diagnostic method by using the Epstein-Barr virus (EBV) capsid antigen IgA antibodies (VCA/IgA). Similar sensitivity (88.5%) and specificity (90.6%) were achieved in another group of 84 samples. Conclusion: SELDI-MS profiling might be a potential tool to identify patients with NPC, particularly at early clinical stages.