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Aims: The addition of extended capecitabine after standard neo/adjuvant chemotherapy shows controversial results in triple-negative breast cancer (TNBC) patients between SYSUCC-001 trial and CIBOMA trial. Patients presents different responses to diverse regimens, and different dose strengths also affect their prognosis. Hence, we tried to investigate whether the benefit from SYSUCC-001 is effected by the strength of previous adjuvant chemotherapy. Methods: We reviewed the neo/adjuvant chemotherapy regimens, dose divide by body surface area, etc. of TNBC patients in SYSUCC-001 trial. Their therapeutic dose were classified into consistent and inconsistent with CIBOMA trial. Besides, we stratified patients into the strong regimen arm (A/EC-T and TA/EC) and medium regimen arm (A/EC, TA/E, CMF, FA/EC, FA/EC-T, and TC) according to their specific neo/adjuvant treatment.Subsequently, we compared differences in baseline characteristics between the strong and medium regimen arms, and further investigated the impact of therapeutic regimens and dose on the survival outcome of TNBC patients in SYSUCC-001 trial(the median follow-up is 61months, interquartile range, 44-82months). Results: A total of 434 TNBC patients were included in this study. Among them, patients who used strong chemotherapy regimen accounted for about 76.74%, and those who used medium regimen accounted for 23.26%. About 32.3% and 52.2% patients received the standard doses of anthracyclines and taxanes separately according to minimum acceptable regimens for chemotherapy in CIBOMA trial. In our analysis we found the dose strength did not affect the DFS in the observe group. However, the standard dose of taxanes improved the DFS in capecitabine group [HR, 2.04 (1.02 - 4.06)]. The interaction analysis showed that the strength of treatment regimenand anthracycline dose did not affect DFS. Whereas, subgroup analysis showed TNBC patients with standard dose of taxanes significantly benefited from capecitabine (P = 0.014). In addition, the standard dose of taxanes could improve DFS. Conclusions: The strength of neo/adjuvant chemotherapy does not affect the curative effect of capecitabine maintenance chemotherapy. The benefits of the SYSUCC-001 study are mainly from one-year capecitabine administration. Moreover, the standard dose of chemotherapy especially taxanes is a positive factor for the effect of capecitabine treatment. So in some special condition, such as patients can’t endure the side effect of the chemotherapy, we’d better reduce the dose of anthracycline not the taxanes.

Epstein-Barr virus (EBV) infection is ubiquitous worldwide and is associated with multiple cancers, including nasopharyngeal carcinoma (NPC). The importance of EBV viral genomic variation in NPC development and its striking epidemic in southern China has been poorly explored. Through large-scale genome sequencing of 270 EBV isolates and two-stage association study of EBV isolates from China, we identified two non-synonymous EBV variants within BALF2 strongly associated with the risk of NPC (odds ratio (OR) = 8.69, P=9.69×10−25 for SNP 162476_C; OR = 6.14, P=2.40×10−32 for SNP 163364_T). The cumulative effects of these variants contributed to 83% of the overall risk of NPC in southern China. Phylogenetic analysis of the risk variants revealed a unique origin in Asia, followed by clonal expansion in NPC-endemic regions. Our results provide novel insights into NPC endemic in southern China and also enable the identification of high-risk individuals for NPC prevention., Editorial Summary Whole-genome sequencing and association analysis of 270 Epstein-Barr virus (EBV) isolates from China identify two non-synonymous EBV variants within BALF2 strongly associated with the risk of nasopharyngeal carcinoma.

Rationale: Epstein-Barr virus (EBV) is associated with multiple malignancies with expression of viral oncogenic proteins and chronic inflammation as major mechanisms contributing to tumor development. A less well-studied mechanism is the integration of EBV into the human genome possibly at sites which may disrupt gene expression or genome stability. Methods: We sequenced tumor DNA to profile the EBV sequences by hybridization-based enrichment. Bioinformatic analysis was used to detect the breakpoints of EBV integrations in the genome of cancer cells. Results: We identified 197 breakpoints in nasopharyngeal carcinomas and other EBV-associated malignancies. EBV integrations were enriched at vulnerable regions of the human genome and were close to tumor suppressor and inflammation-related genes. We found that EBV integrations into the introns could decrease the expression of the inflammation-related genes, TNFAIP3, PARK2, and CDK15, in NPC tumors. In the EBV genome, the breakpoints were frequently at oriP or terminal repeats. These breakpoints were surrounded by microhomology sequences, consistent with a mechanism for integration involving viral genome replication and microhomology-mediated recombination. Conclusion: Our finding provides insight into the potential of EBV integration as an additional mechanism mediating tumorigenesis in EBV associated malignancies.

Extranodal natural killer T-cell lymphoma (nasal type; NKTCL) is an aggressive malignancy strongly associated with Epstein-Barr virus (EBV) infection. However, the role of EBV in NKTCL development is unclear, largely due to the lack of information about EBV genome and transcriptome in NKTCL. Here, using high-throughput sequencing, we obtained whole genome (n = 27) and transcriptome datasets (n = 18) of EBV derived from NKTCL tumor biopsies. We assembled 27 EBV genomes and detected an average of 1,152 single nucleotide variants and 44.8 indels (

The heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8+ T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8+ T and immune-suppressive TNFRSF4+ Treg cells in tumours might derive from peripheral CX3CR1+CD8+ T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3+ DCs. Noteworthily, we observe intensive inter-cell interactions among LAMP3+ DCs, Treg, exhausted CD8+ T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC., Nasopharyngeal carcinoma is a diverse cancer characterised by a heterogeneous microenvironment. Here, the authors use single cell sequencing to analyse the tumour microenvironment in 10 nasopharyngeal carcinoma tumours and identify different cell types including immune-suppressive T regulatory, tolerogenic dendritic, and exhausted CD8 T cells.

Utidelone, a genetically engineered epothilone analogue, has shown promise as a potential treatment for breast cancer in phase 1 and 2 trials. The aim of this phase 3 trial was to compare the efficacy and safety of utidelone plus capecitabine versus capecitabine alone in patients with metastatic breast cancer.We did a multicentre, open-label, superiority, phase 3, randomised controlled trial in 26 hospitals in China. Eligible participants were female patients with metastatic breast cancer refractory to anthracycline and taxane chemotherapy regimens. We randomly assigned participants (2:1) using computer based randomisation and block sizes of 6 to a 21-day cycle of either utidelone (30 mg/mBetween Aug 8, 2014, and Dec 14, 2015, we enrolled and randomly assigned 270 patients to treatment with utidelone plus capecitabine, and 135 to capecitabine alone. Median follow-up for progression-free survival was 6·77 months (IQR 3·81-10·32) for the utidelone plus capecitabine group and 4·55 months (2·55-9·39) for the capecitabine alone group. Median progression-free survival by central review in the utidelone plus capecitabine group was 8·44 months (95% CI 7·95-9·92) compared with 4·27 months (3·22-5·68) in the capecitabine alone group; hazard ratio 0·46, 95% CI 0·36-0·59; p0·0001. Peripheral neuropathy was the most common grade 3 adverse event in the utidelone plus capecitabine group (58 [22%] of 267 patients vs 1 [1%] of 130 patients in the capecitabine alone group). Palmar-plantar erythrodysaesthesia was the most prominent grade 3 adverse event in the capacitabine alone group (in 10 [8%] of 130 patients) and was the next most frequent grade 3 event in the utidelone plus capecitabine group (in 18 [7%] of 267 patients). 16 serious adverse events were reported in the combination therapy group (diarrhoea was the most common, in three [1%] patients) and 14 serious adverse events were reported in the monotherapy group (the most common were diarrhoea, increased blood bilirubin, and anaemia, in two [2%] patients for each event). 155 patients died (99 in the combination therapy arm, 56 in the monotherapy arm). All deaths were related to disease progression except for one in each group (attributed to pericardial effusion in the combination therapy group and dyspnoea in the monotherapy group) that were considered possibly or probably treatment-related.Despite disease progression with previous chemotherapies, utidelone plus capecitabine was more efficacious compared with capecitabine alone for the outcome of progression-free survival, with mild toxicity except for peripheral sensory neuropathy, which was manageable. The findings from this study support the use of utidelone plus capecitabine as an effective option for patients with metastatic breast cancer.Beijing Biostar Technologies, Beijing, China.

SummaryEpstein-Barr virus (EBV) infection is ubiquitous worldwide and associated with multiple cancers including nasopharyngeal carcinoma (NPC). The role of EBV viral genomic variation in NPC development and its striking endemicity in southern China has been poorly explored. Through large-scale genome sequencing and association study of EBV isolates from China, we identified two non-synonymous EBV variants withinBALF2strongly associated with NPC risk (conditionalPvalue 1.75×10-6for SNP162476_C and 3.23×10-13for SNP163364_T), whose cumulative effects contributed to 83% of the overall risk in southern China. Phylogenetic analysis of the risk variants revealed a unique origin in southern China followed by clonal expansion. EBVBALF2haplotype carrying the risk variants were shown to reduce viral lytic DNA replication, as a result potentially promoting viral latency. Our discovery has not only provided insight to the unique endemic pattern of NPC occurrence in southern China, but also paved the way for the identification of individuals at high risk of NPC and effective intervention program to reduce the disease burden in southern China.

// Tao Qin 1,* , Yin-duo Zeng 1,2,* , Ge Qin 1,* , Fei Xu 1,* , Jia-bin Lu 1 , Wen-feng Fang 1 , Cong Xue 1 , Jian-hua Zhan 1 , Xin-ke Zhang 1 , Qiu-fan Zheng 1 , Rou-jun Peng 1 , Zhong-yu Yuan 1 , Li Zhang 1 and Shu-sen Wang 1 1 Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China 2 Sun Yat-sen University Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, P. R. China * These authors have contributed equally to this work Correspondence to: Shu-sen Wang, email: // Li Zhang, email: // Zhong-yu Yuan, email: // Keywords : PD-L1, breast cancer, ER, PR, prognosis, nomogram Received : July 07, 2015 Accepted : August 22, 2015 Published : September 10, 2015 Abstract Background: To investigate the role of PD-L1 expression in tumor recurrence and metastasis in Chinese patients with breast cancer. Methods: Suitable tissue samples were available from 870 patients with breast cancer. Paraffin-embedded tumor sections were stained with PD-L1 antibody. The correlations between PD-L1 expression and clinical characteristics, ER/PR/HER2 status and survival parameters were analyzed. Kaplan-Meier and univariate Cox proportional hazards model analyses were used to compare the survival of patients with high PD-L1 expression and patients with no PD-L1 expression. Results: The median follow-up time was 98 months(range, 17–265 months).The positive rate of PD-L1 expression in breast cancer was 21.7% (189/870). PD-L1 high expression was inversely associated with larger tumor size, higher tumor grade, more positive lymph node number, as well as negative ER and PR status. PD-L1 expression was particularly higher in TNBC compared with non-TNBC, although no statistical significance was observed. Nomogram logistic regression results based on clinical and pathological features showed that the following factors were more likely associated with high PD-L1 expression: patient age younger than 35 years, larger tumor size, lymphovascular invasion and advanced stage. Our data indicated that patients with high PD-L1 expression had poor DFS, DMFS and overall survival compared with those with no PD-L1 expression. Univariate Cox proportional hazards model analysis showed that PD-L1 was an independent prognostic factor for tumor prognosis. Conclusions: PD-L1 expression is an important indicator of unfavorable prognosis in breast cancer patients.

NOP14, which is functionally conserved among eukaryotes, has been implicated in cancer development. Here, we show that NOP14 is poorly expressed in breast cancer cells and invasive breast cancer tissues. In vivo and in vitro studies indicated that NOP14 suppressed the tumorigenesis and metastasis of breast cancer cells. Further investigations revealed that NOP14 enhanced ERα expression and inhibited the Wnt/β-catenin pathway by up-regulating NRIP1 expression. Survival analysis indicated that low NOP14 expression was significantly associated with poor overall survival (P = 0.0006) and disease-free survival (P = 0.0007), suggesting that NOP14 is a potential prognostic factor in breast cancer. Taken together, our findings reveal that NOP14 may suppress breast cancer progression and provide new insights into the development of targeted therapeutic agents for breast cancer.

The existence of cancer stem cells, stem-like cancer cells (SLCCs), or tumor-initiating cells is considered as the cause of tumor formation and recurrence, indicating the importance of studying novel therapy that targets SLCCs. The origin of SLCCs is controversial because of two competing hypotheses: SLCCs are either transformed from tissue adult stem cells or dedifferentiated from transformed progenitor cells. Our previous research demonstrates that SLCCs are inducible by increasing genomic instability in cancer cells. In this study, to block the emergence of SLCCs, aminoethyl isothiourea (AET), a compound that clears free radicals and is used to protect patients from radioactive exposure, was used as an agent that maintains genomic stability in combination with mitomycin C (MMC), a commonly used chemotherapeutic drug that damages DNA. Using a rabbit tumor model with VX2 hepatic carcinoma, we found that MMC alone increased lung metastases and disadvantaged survival outcome, but the combination of MMC and AET reversed this effect and even prolonged overall survival. Moreover, in a VX2 xenograft model by immunocompromised mice, MMC alone enriched tumor-initiating cells, but the administration of MMC in combination with AET eliminated tumor cells effectively. Furthermore, MMC alone enhanced genomic instability, but MMC combined with AET attenuated the extent of genomic instability in primary VX2 tumor tissue. Taken together, our data suggest that the genomic protector AET can inhibit the induction of SLCCs, and this combination treatment by AET and cytotoxic agents should be considered as a promising strategy for future clinical evaluation.

To identify genetic risk factors underlying non-Hodgkin lymphomas (NHLs) from the B cell lineage, we conducted a genome-wide association study (GWAS) of 253 Chinese individuals with B cell NHL (cases) and 1,438 controls and further validation in 1,175 cases and 5,492 controls. We identified a new susceptibility locus, rs6773854, located between BCL6 (encoding B cell lymphoma protein 6) and LPP (encoding lipoma preferred partner) on oncogene-rich chromosome 3q27 that was significantly associated with increased risk of B cell NHL (meta-analysis P = 3.36 × 10⁻¹³, per-allele odds ratio (OR) = 1.44) and with diffuse large B cell lymphoma (DLBCL) in particular (meta-analysis P = 1.14 × 10⁻¹¹, OR = 1.47). We found no evidence of association of rs6773854 with non-B cell NHLs (T cell and natural killer (NK) lineages) (P = 0.17, OR = 1.12) and observed significant heterogeneity between B cell and non-B cell subtypes (Phet = 0.01, I² = 84%). Our results provide insight that germline variation in the intergenic region between BCL6 and LPP has a role in risk of B cell lymphomagenesis.

Summary Background Extranodal natural killer T-cell lymphoma (NKTCL), nasal type, is a rare and aggressive malignancy that occurs predominantly in Asian and Latin American populations. Although Epstein-Barr virus infection is a known risk factor, other risk factors and the pathogenesis of NKTCL are not well understood. We aimed to identify common genetic variants affecting individual risk of NKTCL. Methods We did a genome-wide association study of 189 patients with extranodal NKTCL, nasal type (WHO classification criteria; cases) and 957 controls from Guangdong province, southern China. We validated our findings in four independent case-control series, including 75 cases from Guangdong province and 296 controls from Hong Kong, 65 cases and 983 controls from Guangdong province, 125 cases and 1110 controls from Beijing (northern China), and 60 cases and 2476 controls from Singapore. We used imputation and conditional logistic regression analyses to fine-map the associations. We also did a meta-analysis of the replication series and of the entire dataset. Findings Associations exceeding the genome-wide significance threshold (p −8 ) were seen at 51 single-nucleotide polymorphisms (SNPs) mapping to the class II MHC region on chromosome 6, with rs9277378 (located in HLA-DPB1 ) having the strongest association with NKTCL susceptibility (p=4·21 × 10 −19 , odds ratio [OR] 1·84 [95% CI 1·61–2·11] in meta-analysis of entire dataset). Imputation-based fine-mapping across the class II MHC region suggests that four aminoacid residues (Gly84-Gly85-Pro86-Met87) in near-complete linkage disequilibrium at the edge of the peptide-binding groove of HLA-DPB1 could account for most of the association between the rs9277378*A risk allele and NKTCL susceptibility (OR 2·38, p value for haplotype 2·32 × 10 −14 ). This association is distinct from MHC associations with Epstein-Barr virus infection. Interpretation To our knowledge, this is the first time that a genetic variant conferring an NKTCL risk is noted at genome-wide significance. This finding underlines the importance of HLA-DP antigen presentation in the pathogenesis of NKTCL. Funding Top-Notch Young Talents Program of China, Special Support Program of Guangdong, Specialized Research Fund for the Doctoral Program of Higher Education (20110171120099), Program for New Century Excellent Talents in University (NCET-11-0529), National Medical Research Council of Singapore (TCR12DEC005), Tanoto Foundation Professorship in Medical Oncology, New Century Foundation Limited, Ling Foundation, Singapore National Cancer Centre Research Fund, and the US National Institutes of Health (1R01AR062886, 5U01GM092691-04, and 1R01AR063759-01A1).

Foxp3⁺ regulatory T lymphocytes (Tregs) usually act as an immune suppressor and correlate with poorer survival in malignancies. This study aims to investigate the distribution and characterization of Foxp3(+) subset in peripheral blood mononuclear cells (PBMCs) and tumor tissues from extranodal NK/T cell lymphoma (ENKTL). Our study showed the percentage of Foxp3⁺ subset from PBMC was significantly higher than that of healthy individuals (P

Assessment of antibody responses to Epstein-Barr virus (EBV) antigens has been used to assist in nasopharyngeal carcinoma (NPC) diagnosis by several methods. In this study, we evaluated an in-house Luminex multianalyte profiling (xMAP) technology and commercial enzyme-linked immunosorbent assay (ELISA) kits for serological examination of EBV-specific antibody responses in 135 NPC patients and 130 healthy controls. Four EBV biomarkers were measured: immunoglobulin A (IgA) against viral capsid antigen (VCA), EBV nuclear antigen 1 (EBNA1), diffused early antigen (EA-D), and IgG against EA-D. The sensitivities and specificities of the four markers ranged between 71.5 and 90% for xMAP assays and 80 and 92% for ELISA. Logistic regression analysis revealed that the combined markers in the xMAP assay had overall sensitivity and specificity values of 82% and 92%, respectively. The correlation coefficient ( r ) values for the xMAP assay and ELISA were lowest for IgA-VCA (0.468) and highest for IgA-EBNA1 (0.846); for IgA-EA-D and IgG-EA-D, the r values were 0.719 and 0.798, respectively. The concordances of the two methods for NPC discrimination were good (79 to 88%). Our results suggest that both the xMAP assay and ELISA are satisfactory for EBV antibody evaluation when multiple antigens are included.

Aim. Data from The Cancer Genome Atlas (TCGA) show that the ZNF703 gene amplifies and overexpresses in head and neck squamous cell carcinomas (HNSCC). However, the clinical relevance of this observation in HNSCC is unclear. The purpose of this study was to clarify the expression of ZNF703 protein and its prognostic effect on HNSCC.Methods. Two hundred ten HNSCC patients from Sun Yat-Sen University Cancer Center with complete survival follow-up were included in this study. Tumor samples from primary sites were collected. The expression of the ZNF703 protein was tested by immunohistochemistry (IHC).Results. The high expression of ZNF703 in HNSCC tumor tissues was significantly higher than that of the matched noncancerous tissues (48.6% versus 11.6%,P<0.001). ZNF703 overexpression was correlated with tumor position (laryngeal carcinoma) and recurrence (allP<0.05). Multivariate analysis revealed that ZNF703 protein overexpression was an independent prognostic factor (P=0.022, hazard ratio = 1.635, 95% CI 1.073–2.493) in HNSCC patients.Conclusion. ZNF703 overexpression is associated with adverse prognosis in HNSCC, which might be a novel biomarker of HNSCC.

Zhong-Yu Yuan,1–3,* Ting Dai,1,2,* Shu-Sen Wang,1–3 Rou-Jun Peng,1–3 Xing-Hua Li,1,2 Tao Qin,1–3 Li-Bing Song,1,2 Xi Wang1,2,41State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China; 2Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; 3Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China; 4Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China *These authors contributed equally to this work Background: Patients with triple-negative breast cancer (TNBC) present a higher probability of distant metastasis and lack of effective targeted therapy. ETS translocation variant 4 (ETV4) is an ETS (E-26) transcription factor and has been associated with tumor metastasis. However, the clinical and functional significance of ETV4 in TNBC still remains unclear. Methods: A human tumor metastasis polymerase chain reaction array was used to profile differential expression of tumor metastasis-related genes in TNBC tissue. Real-time reverse transcription and Western blot analyses were performed to verify ETV4 expression in TNBC cells and tissue. Immunohistochemistry was used to detect expression of ETV4 protein in 135 TNBC tissue samples for association between ETV4 protein expression and clinical outcomes. Results: A total total of eight upregulated (CCL7, KISS1, MET, MMP7, NR4A3, ETV4, TIMP3, and TSHR) and three downregulated (ITGA7, SSTR, and MMP2) genes were identified between TNBC tissue and the luminal subtype of breast cancer tissue. ETV4 messenger ribonucleic acid was more than five-fold upregulated in TNBC tissue compared with the control tissue. ETV4 overexpression was found in 57.0% of 135 TNBC cases. Overexpression of ETV4 protein was associated with an advanced stage and a higher proportion of positive lymph node and lymphovascular invasion. Patients with an ETV4-overexpressed tumor had a significantly higher risk of developing distant metastasis (P

Purpose: This study aimed to assess possible interactive effects of coping styles and psychological stress on depression and anxiety symptoms in Chinese women shortly after diagnosis of breast cancer. Methods: Four hundred and one patients with breast cancer were face-to-face interviewed by trained research staff according to a standardized questionnaire including information on socio-demographic characteristics, psychological stress, coping styles, and anxiety and depressive symptoms. Interactive effects were assessed by hierarchical multiple regression analyses. Results: There were significant associations of the four domains of psychological stress with anxiety and depressive symptoms except for the relationship between "worrying about health being harmed" and depressive symptoms. "Abreaction coping behavior" and "escaping coping behavior" significantly increased the level of both anxiety and depressive symptoms; whereas an "active coping style" reswulted in significant decrease. The interaction of "active coping behavior" with "worrying about health being harmed" significantly increased the risk of the anxiety symptoms, while adopting "self-relaxing coping behavior" was associated with significant decrease. The interaction of "worry about daily life and social relationship being restricted" with "escaping coping behavior" significantly increased the risk of the depressive symptoms. Conclusions: The results of this study suggest that certain coping styles might moderate the association of psychological stress with anxiety and depressive symptoms in Chinese women with breast cancer.

The aim of the present study was to assess the association of psychological stress and social support with anxiety and depressive symptoms in Chinese newly diagnosed breast cancer patients.Four hundred and one patients with breast cancer were recruited. Their demographic characteristics, psychological stress and social support were determined with a structured questionnaire, and their anxiety and depressive symptoms were assessed with the Hospital Anxiety and Depression Scale.Psychological stressors caused by breast cancer diagnosed originated from five major sources, as determined by factor analysis. These included "Worrying about health being harmed, " "Fear of decline of physical function, " "Fear of work being harmed, " "Worry about daily life and social relationship being restricted, " and "Fear of family being harmed. " Hierarchical linear regression analysis indicated that, after adjusting for gender, age, marital status, educational level, and duration of illness, solid social support can alleviate such symptoms.The results of this study suggest that there are strong associations between patients' needs and psychological distress with newly diagnosed breast cancer. Social support might affect these associations in Chinese women with breast cancer.

The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial. We compared the characteristics and prognosis of bilateral breast cancer and unilateral breast cancer.Our study included 4,183 patients with breast cancer who were treated at Sun Yat-sen University Cancer Center between January 1, 2000, and December 31, 2007. Bilateral breast cancer was categorized as synchronous (within 3 months) or metachronous (diagnosed after 3 months of first cancer). SPSS was used for data analysis.106 (2.5%) and 31 (0.7%) patients were diagnosed with metachronous and synchronous bilateral cancer. Women with bilateral cancer had more frequent postmenopause, HER-2 negativity, and advanced disease than in patients with unilateral cancer. Young age at diagnosis, invasive lobular carcinoma, ER/PR negativity, HER-2 positivity, radiation, large tumor size (T5 cm), and stage III disease of the first cancer were risk factors for contralateral cancer. The 5-year disease-free survival and overall survival rates were 76 and 83% for unilateral cancer, while 32 and 72% for bilateral cancer (P = 0.000 for both).Bilateral cancer was associated with shorter disease-free survival and overall survival than unilateral cancer. The prognosis of metachronous bilateral cancer, especially those diagnosed within 2 years after the first cancer was significantly worse than synchronous bilateral cancer.

Epstein-Barr virus (EBV)-encoded molecules have been detected in the tumor tissues of several cancers, including nasopharyngeal carcinoma (NPC), suggesting that EBV plays an important role in tumorigenesis. However, the nature of EBV with respect to genome width in vivo and whether EBV undergoes clonal expansion in the tumor tissues are still poorly understood. In this study, next-generation sequencing (NGS) was used to sequence DNA extracted directly from the tumor tissue of a patient with NPC. Apart from the human sequences, a clinically isolated EBV genome 164.7 kb in size was successfully assembled and named GD2 (GenBank accession number HQ020558 ). Sequence and phylogenetic analyses showed that GD2 was closely related to GD1, a previously assembled variant derived from a patient with NPC. GD2 contains the most prevalent EBV variants reported in Cantonese patients with NPC, suggesting that it might be the prevalent strain in this population. Furthermore, GD2 could be grouped into a single subtype according to common classification criteria and contains only 6 heterozygous point mutations, suggesting the monoclonal expansion of GD2 in NPC. This study represents the first genome-wide analysis of a clinical isolate of EBV directly extracted from NPC tissue. Our study reveals that NGS allows the characterization of genome-wide variations of EBV in clinical tumors and provides evidence of monoclonal expansion of EBV in vivo . The pipeline could also be applied to the study of other pathogen-related malignancies. With additional NGS studies of NPC, it might be possible to uncover the potential causative EBV variant involved in NPC.

Anaplastic T-cell lymphoma in children and adolescents is an aggressive malignant non-Hodgkin's lymphoma (NHL). The optimal treatment regimen needs to be investigated. This study was to evaluate the efficacy of modified B-NHL-BFM-90 protocol on anaplastic T-cell lymphoma in children and adolescents.From October 2002 to January 2008, 18 untreated anaplastic T-cell lymphoma patients aged less than 16 years were enrolled, and treated with modified B-NHL-BFM-90 protocol including cyclophosphamide, vincristine, ifosfamide, etoposide, adriamycin, HD-methotrexate, vindesine, dexamethasone, cytarabine/HD-cytarabine. Intrathecal injection was given every course.Of the 18 patients, 15 (83.3%) achieved complete remission (CR), and three (16.7%) achieved partial remission (PR). The patients were followed up for 4-68 months (median, 31 months). The 3-year event-free survival (EFS) rates were (87.4+/-8.4)% for all patients, 100% for stage II patients, and (85.1+/-9.7)% for stage III/IV patients; 100% for low risk group, (88.9+/-10.5)% for moderate risk group, and (80.0+/-17.9)% for high risk group. Most patients suffered from grade 3-4 myelosuppression and recovered after active support care. One patient with stage IV disease received autologous peripheral blood stem cell transplantation (PBSCT) after CR and was still alive. Two patients had tumor relapsed and died at three and five months after off treatment, respectively.Modified B-NHL-BFM-90 protocol, with tolerable toxicity, is an effective treatment regimen for anaplastic T-cell lymphoma in children and adolescents. It should be used in experienced cancer centers and hematological units.

T-cell non-Hodgkin lymphoma was heterogeneous and relatively high incident in our country. It's response and prognosis were poor. This study was to analyze clinical feature and survival of T-NHL.Records of 103 cases with T-NHL, treated from Dec 1998 to Dec 2004 in Cancer Center of Sun Yat-sen University, were retrospectively analyzed. All the patients were classified according to WHO 2001 Classification Criteria.Median age of the whole group was 35 (ranged 2-78) years-old. Of the 103 cases, 68 were male, 35 were female; 25 (24.3%) received chemoradiotherapy, 70 (68.0%) received chemotherapy alone, 3 received radiotherapy and 5 received stem cell transplantation after complete remission. Median survival was 24.1 (ranged 0.8-84) months. 5-year survival rate was 24.3%. Kaplan-Meier analysis discovered that age60 years, advanced stage (stage II, IV), extranodal involvement, bulky disease, B symptom, performance status (PS)or = 2, LDH elevated, hypoalbumin, median-high IPI (IPIor = 2) were bad to prognosis, but Cox regression found that ageor = 60 years, performance status (PS)or = 2S, hypoalbumin were the independent bad factors to prognosis.This study proved that age, albumin, PS were the independent factors to prognosis.

The prognosis of breast cancer patients with liver metastasis is poor. How to improve treatment efficacy and prolong survival of these patients is a challenge in clinic. This study was to explore the efficacy of chemotherapy and transcatheter arterial chemoembolization (TACE) on breast cancer patients with liver metastasis, and analyze prognostic factors.Clinical data of 98 breast cancer patients with liver metastasis, treated from 1996 to 2005 in Cancer Center of Sun Yat-sen University, were analyzed retrospectively. The prognostic factors correlated to clinical features and treatment approaches were determined using Cox multivariate model.The total response rate was 45.9% for all patients, 48.6% for the 74 patients received systemic chemotherapy, 23.1% for the 13 patients received TACE, and 54.6% for the 11 patients received chemotherapy plus TACE. At a median follow-up of 17 months (3-56 months), the 1-, 2-, 3-, and 4-year survival rates were 36%, 19%, 13%, and 3%, respectively; the median survival was 17 months (3-56 months), and the progression-free survival was 6 months (0-50 months).The combination of systemic chemotherapy and TACE may prolong the survival of breast cancer patients with liver metastasis.

Purpose This study investigated the clinicopathological features of operable breast cancer lesions located in different hemispheres of the breast and determined related survival outcomes. Methods Data from 5,330 patients with invasive ductal carcinoma were retrospectively analyzed based on tumor location. Results The median follow-up time was 68 months (range, 18-176 months). Patients with breast cancer located in the outer hemisphere of the breast had lesions with more advanced nodal stages and more frequently received adjuvant chemotherapy than patients with breast cancer in the inner hemisphere. The 5-year disease-free survival (DFS) rates of patients with tumors located in outer versus inner hemispheres were 81.5% and 77.0%, respectively (p=0.004); the overall survival (OS) rates were 90.7% and 88.8%, respectively (p

Two kinds of home-produced docetaxel in China, injection Yiyoutasai and injection Aisu, have the same structure. Data from preclinical study had shown that injection Yiyoutasai has the same pharmacokinetics and toxicity as injection Aisu. This study was to evaluate the efficacy and toxicity of injection Yiyoutasai in treating advanced breast cancer.Eligible breast cancer patients were enrolled and randomly assigned to study group and control group, and received injection of 75 mg/m(2) Yiyoutasai or Aisu, respectively. The injections were repeated every 3 weeks. All patients received at least 2 cycles. The efficacy of Yiyoutasai and Aisu were evaluated after treatment.A total of 67 patients were enrolled: 33 in study group, and 34 in control group. Of the 31 evaluable cases in study group, 1 achieved complete remission (CR), 9 achieved partial remission (PR), 11 had stable disease (SD), and 10 had progressive disease (PD); the total response rate was 22.22%. There were 1 CR, 5 PR, 19 SD, and 9 PD in control group; the total response rate was 15.15%. There was no significant difference between the 2 groups (P=0.662). The median follow-up was 16.5 months (8-28 months). In study group, the median progression-free survival time was 6.2 months (2-12 months), the 1-year survival rate was 68.51%, and the 2-year survival rate was 40.12%; in control group, the median progression-free survival time was 7.1 months (2.3-11 months), the 1-year survival rate was 65.23%, and the 2-year survival rate was 39.71%. There was no significant difference between the 2 groups (P=0.102, 0.098, 0.089, respectively). Common adverse events were myelosuppression, transient transaminase elevation, and alopecia. One patient in study group suffered from severe allergic reaction after infusion, 1 in control group suffered from whole body edema.Yiyoutasai and Aisu have similar efficacy on and toxicity to advanced breast cancer patients.

Toxicities and their severities vary among advanced gastric cancer patients when they receive the same regimen containing continuous infusion of 5-fluorouracil (5-FU). Dihydropyrimidine dehydrogenase (DPD) is the key rate-limiting enzymes which is closely related to toxicities of 5-FU in chemotherapy. This study was to explore the relationship between activity of DPD and concentration of 5-FU, and their correlation to adverse events among advanced gastric cancer patients treated with the same regimen containing 5-FU continuous infusion.Patients received the same regimen (intravenous injection of paclitaxel 75 mg/m(2), leucovorin 200 mg/m(2) and 5-FU 375 mg/m(2), continuous infusion of 5-FU 2.5 g/m2 for 46 hours every two weeks). The peripheral blood was collected from 36 patients with advanced gastric cancer before and after chemotherapy to detect the activity of DPD and concentration of 5-FU by high-performance liquid chromatography (HPLC). Adverse events were assessed every cycle.Serum activity of DPD revealed a unimodel distribution, which globally fits to a guassian distribution (range 1.56-6.01). Mean and median DPD activity values were 2.38 and 2.13, respectively. No total DPD deficiency was found in the patients. The concentration of 5-FU varied from 179.2 microg/L to 1 589.2 microg/L, which demonstrated normality distribution after a logarithmic transformation was applied. The DPD activity was inversely correlated with 5-FU concentration (r=-0.376, P=0.024). The patients with low activity of DPD were more frequently suffering from severe diarrhea, mucositis, and myelosuppression. And high level of 5-FU concentration led to the increase of adverse events.Pre-chemotherapy DPD activity and 5-FU concentration during chemotherapy vary among gastric cancer patients, which may help to prevent severe toxicities during the treatment.

Vascular endothelial growth factor (VEGF) signal pathway is a hot spot in recent tumor research, but its role in rhabdomyosarcoma (RMS) has rarely been reported, and its mechanism is unclear. This study was to investigate the expression of VEGF and its receptors (VEGFR) in RMS cell line RH4 to reveal the mechanism of VEGF signal pathway, and explore the therapeutic value of Avastin in RMS in vitro.Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of VEGF, VEGFR1, VEGFR2, and VEGFR3 mRNA in RH4 cells. ELISA was used to detect the concentration of VEGF in supernatant. Western blot was used to detect the expression of VEGFR1 protein. The effects of VEGF and Avastin on RH4 cell growth were evaluated by direct cell counting.RH4 cells expressed VEGF at a high level and secreted VEGF to culture media. RH4 cells only expressed VEGFR1, did not express VEGFR2 and VEGFR3. VEGF promoted the growth of RH4 cells in a dose-dependent manner within a concentration range of 0-100 ng/ml, this effect could be blocked by 10-40 microg/ml Avastin.VEGF can promote the growth of RMS cell through VEGFR1, and this effect can be blocked by Avastin.