Serglycin in human cancers

Serglycin belongs to a family of small proteoglycans with Ser-Gly dipeptide repeats,and it is modified with different types of glycosaminoglycan side chains.Intracellular serglycin affects the retention and secretion of proteases,chemokines,or other cytokines by physically binding to these factors in secretory granules.Extracellular serglycin has been found to be released by several types of human cancer cells,and it is able to promote the metastasis of nasopharyngeal carcinoma cells.Serglycin can bind to CD44,which is another glycoprotein located in cellular membrane.Serglycin's function of promoting cancer cell metastasis depends on glycosylation of its core protein,which can be achieved by autocrine as well as paracrine secretion mechanisms.Further investigations are warranted to elucidate serglycin signaling mechanisms with the goal of targeting them to prevent cancer cell metastasis.

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.

Locoregional radiotherapy in patients with distant metastases of nasopharyngeal carcinoma at diagnosis

Systemic chemotherapy is the basic palliative treatment for metastatic nasopharyngeal carcinoma(NPC); however, it is not known whether locoregional radiotherapy targeting the primary tumor and regional lymph nodes affects the survival of patients with metastatic NPC. Therefore, we aimed to retrospectively evaluate the benefits of locoregional radiotherapy. A total of 408 patients with metastatic NPC were included in this study. The mortality risks of the patients undergoing supportive treatment and those undergoing chemotherapy were compared with that of patients undergoing locoregional radiotherapy delivered alone or in combination with chemotherapy. Univariate and multivariate analyses were conducted. The contributions of independent factors were assessed after adjustment for covariates with significant prognostic associations (P<0.05). Both locoregional radiotherapy and systemic chemotherapy were identified as significant independent prognostic factors of overall survival(OS). The mortality risk was similar in the group undergoing locoregional radiotherapy alone and the group undergoing systemic chemotherapy alone [multi-adjusted hazard ratio(HR)=0.9, P=0.529]; this risk was 60% lower than that of the group undergoing supportive treatment(HR=0.4, P=0.004) and 130% higher than that of the group undergoing both systemic chemotherapy and locoregional radiotherapy(HR=2.3, P<0.001). In conclusion, locoregional radiotherapy, particularly when combined with systemic chemotherapy, is associated with improved survival of patients with metastatic NPC.

Cancer metastasis: issues and challenges

Metastasis is the major cause of treatment failure in cancer patients and of cancer?related deaths.This editorial discusses how cancer metastasis may be better perceived and controlled.Based on big?data analyses,a collection of150 important pro?metastatic genes was studied.Using The Cancer Genome Atlas datasets to re?analyze the effect of some previously reported metastatic genes—e.g.,JAM2,PPARGC1A,SIK2,and TRAF6—on overall survival of patients with renal and liver cancers,we found that these genes are actually protective factors for patients with cancer.The role of epithelial–mesenchymal transition(EMT)in single?cell metastasis has been well?documented.However,in metastasis caused by cancer cell clusters,EMT may not be necessary.A novel role of epithelial marker E?cadherin,as a sensitizer for chemoresistant prostate cancer cells by inhibiting Notch signaling,has been found.This editorial also discusses the obstacles for developing anti?metastatic drugs,including the lack of high?throughput technologies for identifying metastasis inhibitors,less application of animal models in the pre?clinical evaluation of the leading com?pounds,and the need for adjustments in clinical trial design to better reflect the anti?metastatic efficacy of new drugs.We are confident that by developing more effective high?throughput technologies to identify metastasis inhibitors,we can better predict,prevent,and treat cancer metastasis.

Revisiting tumor angiogenesis:vessel co-option,vessel remodeling,and cancer cell-derived vasculature formation

Tumor growth and metastasis depend on the establishment of tumor vasculature to provide oxygen,nutrients,and other essential factors.The well-known vascular endothelial growth factor(VEGF) signaling is crucial for sprouting angiogenesis as well as recruitment of circulating progenitor endothelial cells to tumor vasculature,which has become therapeutic targets in clinical practice.However,the survival benefits gained from targeting VEGF signaling have been very limited,with the inevitable development of treatment resistance.In this article,we discuss the most recent findings and understanding on how solid tumors evade VEGF-targeted therapy,with a special focus on vessel co-option,vessel remodeling,and tumor cell-derived vasculature establishment.Vessel co-option may occur in tumors independently of sprouting angiogenesis,and sprouting angiogenesis is not always required for tumor growth.The differences between vessel-like structure and tubule-like structure formed by tumor cells are also introduced.The exploration of the underlying mechanisms of these alternative angiogenic approaches would not only widen our knowledge of tumor angiogenesis but also provide novel therapeutic targets for better controlling cancer growth and metastasis.

At-home cancer screening:a solution for China and other developing countries with a large population and limited number of healthcare practitioners

Five-year survival rate for patients with all cancers combined, in China, is only 30.9%, which is much lower than those in developed countries. The three main reasons for the low cancer curative rates in China include differences in the spectrum of cancer types, in early detection rates, and in the percentage of cancer patients receiving standardized treatment between China and developed countries.The most important mechanism for improving the curative rate is to improve early detection rates of major cancers in China using novel and affordable technologies that can be operated at home by the patients themselves.This attempt could be helpful in setting up a practical example for other developing countries with limited medical resources and a limited number of healthcare practitioners.

A new prognostic histopathologic classification of nasopharyngeal carcinoma

Background:The current World Health Organization(WHO) classification of nasopharyngeal carcinoma(NPC) con?veys little prognostic information.This study aimed to propose an NPC histopathologic classification that can poten?tially be used to predict prognosis and treatment response.Methods:We initially developed a histopathologic classification based on the morphologic traits and cell differentia?tion of tumors of 2716 NPC patients who were identified at Sun Yat?sen University Cancer Center(SYSUCC)(training cohort).Then,the proposed classification was applied to 1702 patients(retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients(prospective validation cohort) from SYSUCC.The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes.We used Cox proportional hazards models to estimate hazard ratios(HRs) with 95% confidence intervals(CI) for overall survival(OS).Results:The 5?year OS rates for all NPC patients who were diagnosed with epithelial carcinoma(EC;3708 patients),mixed sarcomatoid?epithelial carcinoma(MSEC;1247 patients),sarcomatoid carcinoma(SC;823 patients),and squamous cell carcinoma(SCC;253 patients) were 79.4%,70.5%,59.6%,and 42.6%,respectively(P < 0.001).In mul?tivariate models,patients with MSEC had a shorter OS than patients with EC(HR = 1.44,95% CI = 1.27–1.62),SC(HR = 2.00,95% CI = 1.76–2.28),or SCC(HR = 4.23,95% CI = 3.34–5.38).Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC(HR 49–0.75),and possibly for those with SCC(HR = 0.67,95% CI = 0.56–0.80),MSEC(HR = 0.58,95% CI = 0..74–1.28).= 0.63;95% CI = 0.40–0.98),but not for patients with SC(HR = 0.97,95% CI = 0Conclusions:The proposed classification offers more information for the prediction of NPC prognosis compared with the WHO classification and might be a valuable tool to guide treatment decisions for subtypes that are associ?ated with a poor prognosis.

Favorable prognosis of female patients with nasopharyngeal carcinoma

The female sex is traditionally considered a favorable prognostic factor for nasopharyngeal carcinoma (NPC). However, no particular study has reported this phenomenon. To explore the prognostic impact of gender on patients with NPC after definitive radiotherapy, we reviewed the clinical data of 2,063 consecutive patients treated between 1st January 2000 and 31st December 2003 in the Sun Yat-sen University Cancer Center. The median follow-up for the whole series was 81 months. The female and male patients with early stage disease comprised 49.4% and 28.1% of the patient population, respectively. Both the 5-year overall survival (OS) and disease-specific survival (DSS) rates of female patients were significantly higher than those of male patients (OS: 79% vs. 69%, P < 0.001; DSS: 81% vs. 70%, P < 0.001). For patients with locoregionally advanced NPC, the 5-year OS and DSS rates of female vs. male patients were 74% vs. 63% (P < 0.001) and 76% vs. 64%, respectively (P < 0.001). A multivariate analysis showed that gender, age, and TNM stage were independent prognostic factors for the 5-year OS and DSS of NPC patients. The favorable prognosis of female patients is not only attributed to the early diagnosis and treatment but might also be attributed to some intrinsic factors of female patients.

The rationale for preventing cancer cachexia：targeting excessive fatty acid oxidation

Cachexia commonly occurs at the terminal stage of cancer and has largely unclear molecular mechanisms.A recent study published in Nature Medicine,entitled "Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia," reveals that cachectic cancer cells can secrete multiple cytokines that induce excessive fatty acid oxidation,which is responsible for muscle loss in cancer cachexia.Inhibition of fatty acid oxidation using etomoxir can increase muscle mass and body weight in cancer cachexia animal models.The usage of stable cachexia animal models is also discussed in this research highlight.

Wnt3a:functions and implications in cancer

Wnt3a,one of Wnt family members,plays key roles in regulating pleiotropic cellular functions,including self-renewal,proliferation,differentiation,and motility.Accumulating evidence has suggested that Wnt3 a promotes or suppresses tumor progression via the canonical Wnt signaling pathway depending on cancer type.In addition,the roles of Wnt3 a signaling can be inhibited by multiple proteins or chemicals.Herein,we summarize the latest findings on Wnt3 a as an important therapeutic target in cancer.

Repressing malic enzyme 1 redirects glucose metabolism,unbalances the redox state,and attenuates migratory and invasive abilities in nasopharyngeal carcinoma cell lines

A large amount of nicotinamide adenine dinucleotide phosphate(NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells.Malic enzyme 1(ME1)-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool.ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis.In the present study,we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma(NPC) cells.High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells.However,there were no obvious changes in the other two pathways for glucose metabolism:glycolysis and oxidative phosphorylation.Interestingly,NADPH was decreased under low-glucose condition in ME1-repressed cells relative to wild-type cells,whereas no significant difference was observed under high-glucose condition.ME1-repressed cells had significantly decreased tolerance to low-glucose condition.Moreover,NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress.Furthermore,diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein.Collectively,these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.

Air pollution:a smoking gun for cancer

Once considered a taboo topic or stigma,cancer is the number one public health enemy in the world.Once a product of an almost untouchable industry,tobacco is indisputably recognized as a major cause of cancer and a target for anticancer efforts.With the emergence of new economic powers in the world,especially in highly populated countries such as China,air pollution has rapidly emerged as a smoking gun for cancer and has become a hot topic for public health debate because of the complex political,economic,scientific,and technologic issues surrounding the air pollution problem.This editorial and the referred articles published in this special issue of the Chinese Journal of Cancer discuss these fundamental questions.Does air pollution cause a wide spectrum of cancers?Should air pollution be considered a necessary evil accompanying economic transformation in developing countries?Is an explosion of cancer incidence coming to China and how soon will it arrive?What must be done to prevent this possible human catastrophe?Finally,the approaches for air pollution control are also discussed.

Familial nasopharyngeal carcinomas possess distinguished clinical characteristics in southern China

Objective： To compare clinical characteristics between familial nasopharyngeal carcinomas（NPCs） and sporadic NPCs in Guangdong province, China, a high-risk area.Methods： Between 1991 and 2001, 993 NPC patients treated at the Cancer Center of Sun Yat-Sen University in Guangdong were randomly selected as probands. Information about NPC among the probands＇ relatives and other information were obtained from a retrospective review of the patients＇ medical records. The patients were divided into sporadic NPC, low-frequency familial NPC（one NPC patient in addition to the proband in three generations）, and high-frequency familial NPC（2 or more additional NPC patients in three generations） groups. Pathological and clinical characteristics were compared among these groups.Results： Of the 993 patients, 131（13.2%） had a familial history of NPC. The average age at diagnosis was the lowest in the high-frequency familial NPC group（39 years; P=0.048）. Although the overall survival（OS）, distant metastasis-free survival（DMFS）, and disease-free survival（DFS） rates did not differ between familial and sporadic NPCs, the locoregional recurrence-free survival（LRFS） rate increased in the order sporadic NPCs, low-frequency familial NPCs, and high-frequency familial NPCs（P=0.009）, with 5-year rates of 70%, 83%, and 87%, respectively. Multivariate analysis showed that family history of NPC was an independent favorable prognostic factor for LRFS, with adjusted hazard ratio（a HR） of 0.548, 95% CI（0.342-0.878）. The high LRFS for familial NPCs was mainly noted among young, advanced-stage patients who received continuous radiation treatment.Conclusions： Genetic factors may play an important role in the etiology of high-frequency familial NPC and underlie the early age of onset and sensitivity to radiotherapy.

For robust big data analyses:a collection of 150 important pro-metastatic genes

Metastasis is the greatest contributor to cancer?related death.In the era of precision medicine,it is essential to predict and to prevent the spread of cancer cells to significantly improve patient survival.Thanks to the application of a variety of high?throughput technologies,accumulating big data enables researchers and clinicians to identify aggressive tumors as well as patients with a high risk of cancer metastasis.However,there have been few large?scale gene collection studies to enable metastasis?related analyses.In the last several years,emerging efforts have identi?fied pro?metastatic genes in a variety of cancers,providing us the ability to generate a pro?metastatic gene cluster for big data analyses.We carefully selected 285 genes with in vivo evidence of promoting metastasis reported in the literature.These genes have been investigated in different tumor types.We used two datasets downloaded from The Cancer Genome Atlas database,specifically,datasets of clear cell renal cell carcinoma and hepatocellular carcinoma,for validation tests,and excluded any genes for which elevated expression level correlated with longer overall survival in any of the datasets.Ultimately,150 pro?metastatic genes remained in our analyses.We believe this collection of pro?metastatic genes will be helpful for big data analyses,and eventually will accelerate anti?metastasis research and clinical intervention.

The Chinese Journal of Cancer is indexed in Science CitationIndex(SCI) Expanded

On July 22,2014,the Chinese Journal of Cancer(CJC)received a notification from Thomson Reuters that the publications of our journal starting from 2012 have been accepted for coverage in Science Citation Index Expanded,available at the Web of Science,Core Collection,Biological Abstracts,and Biosis Previews.What this means in practical terms is that CJC will receive its first official impact factor(IF)in 2015.This is an important milestone in the history

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.

Defeating cancer:the 150 most important questions in cancer research and clinical oncology

Despite all the human efforts and monetary investment over the last few decades,cancer is still a devastating threat to our life expectancy and quality of life in many parts of the world.The etiology of cancer varies.The genetic and epigenetic causes of cancer are heterogeneous and multifaceted.Early detection is still a

Our DREAM of defeating cancer: a summary of the 3rd Guangzhou International Symposium on Oncology

Every 6 seconds,someone dies from cancer somewhere in the world.Every 13 seconds,a cancer patient dies in China.Cancer is currently the biggest threat to life around the world and a critical burden to China.To address this problem,it is especially important for scientists and physicians to remain abreast of cutting edge research and progress in the treatment of this disease.The 3rd Guangzhou International Symposium on Oncology

Twenty years after:the beautiful hypothesis and the ugly facts

The limited clinical benefits from current antiangiogenic therapy for cancer patients have triggered some critical thoughts and insightful investigations aiming to further elucidate the relationship between vessels and cancer.Tumors need blood perfusion but there are mounting evidences that angiogenesis alone does not explain it in all the neoplasms.In this editorial,for a special issue on tumor and vessels published in the Chinese Journal of Cancer,we briefly introduce the history of the evidences that solid tumors can sometimes obtain blood perfusion by alternative approaches other than sprouting angiogenesis,i.e.,vessel co-option and vasculogenic mimicry.This editorial provides also the links to several most recently published discoveries and hypotheses on tumor interaction with blood vessels.

High incidence of nasopharyngeal cancer: similarity for 60% of mitochondrial DNA signatures between the Bidayuhs of Borneo and the Bai-yue of Southern China

Populations in Southern China (Bai-yue) and Borneo (Bidayuh) with high incidence of nasopharyngeal cancer (NPC) share similar mitochondrial DNA signatures, supporting the hypothesis that these two populations may share the same genetic predisposition for NPC, which may have first appeared in a common ancestral reference population before the sea levels rose after the last ice age.