Randomized controlled trial of cognitive behavioural therapy for depressive and anxiety symptoms in Chinese women with breast cancer.

Depressive and anxiety symptoms are frequently observed in breast cancer survivors. To date, few randomized controlled trials have been conducted on the efficacy of cognitive behavioural therapy (CBT) for depressive and anxiety symptoms in Chinese population. This study aims to verify the efficacy of CBT in Chinese breast cancer survivors. Women (n = 392) with breast cancer were randomly assigned to 3 groups: CBT (n = 98), self-care management (SCM, n = 98), and usual care (UC, n = 196) using the proportion 1:1:2. Women in the CBT and SCM groups received a series of nine sessions for 12 weeks, while women in the UC group received their usual medical care only. Depressive and anxiety symptoms were assessed using the Hamilton Depression Rating Scale (HAMD) and the Hamilton Anxiety Scale (HAMA) score at baseline, 2, 4, 8, 12, 16, and 24 weeks. A significant intergroup difference was found in the HAMD and HAMA scores. Women in the CBT group showed significantly less depressive and anxiety symptoms compared with women in the SCM and UC groups over time. In conclusion, this study supports the efficacy of CBT for depressive and anxiety symptoms in Chinese breast cancer survivors.

Effects of cognitive behavioral therapy for depression on improving insomnia and quality of life in Chinese women with breast cancer: results of a randomized, controlled, multicenter trial.

PURPOSE: Cognitive behavioral therapy (CBT) for depression had been found to be effective in reducing depressive and anxiety symptoms in breast cancer survivors. It is not known whether CBT for depression would also improve insomnia and quality of life (QOL). The aim of this study was to investigate whether CBT for depression would improve insomnia and QOL in a randomized controlled multicenter trial. PATIENTS AND METHODS: In this study, breast cancer survivors (n=392) were randomly allocated to the following three groups: CBT (n=98), self-care management (SCM, n=98), and usual care (UC, n=196) in a ratio of 1:1:2. CBT and SCM received a series of nine sessions for 12 weeks, whereas UC received UC only. Insomnia and QOL were evaluated using Athens Insomnia Scale (AIS) and Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire at baseline, 4, 12, and 24 weeks. RESULTS: There was a significant intergroup difference in AIS and FACT-B scores (both P<0.01). CBT showed less insomnia problems and better overall QOL compared with those in SCM and UC (both P<0.01). No significant differences were found between SCM and UC in insomnia problems and overall QOL. Moreover, the effects of CBT on insomnia and QOL were maintained during the follow-up period. CONCLUSION: CBT for depression can be effective in improving insomnia problems and QOL in the Chinese breast cancer survivors.

HIV Care and Viral Suppression During the Last Year of Life: A Comparison of HIV-Infected Persons Who Died of HIV-Attributable Causes With Persons Who Died of Other Causes in 2012 in 13 US Jurisdictions.

BACKGROUND: Little information is available about care before death among human immunodeficiency virus (HIV)-infected persons who die of HIV infection, compared with those who die of other causes. OBJECTIVE: The objective of our study was to compare HIV care and outcome before death among persons with HIV who died of HIV-attributable versus other causes. METHODS: We used National HIV Surveillance System data on CD4 T-lymphocyte counts and viral loads within 12 months before death in 2012, as well as on underlying cause of death. Deaths were classified as "HIV-attributable" if the reported underlying cause was HIV infection, an AIDS-defining disease, or immunodeficiency and as attributable to "other causes" if the cause was anything else. Persons were classified as "in continuous care" if they had ≥2 CD4 or viral load test results ≥3 months apart in those 12 months and as having "viral suppression" if their last viral load was <200 copies/mL. RESULTS: Among persons dying of HIV-attributable or other causes, respectively, 65.28% (2104/3223) and 30.88% (1041/3371) met AIDS criteria within 12 months before death, and 33.76% (1088/3223) and 50.96% (1718/3371) had viral suppression. The percentage of persons who received ≥2 tests ≥3 months apart did not differ by cause of death. Prevalence of viral suppression for persons who ever had AIDS was lower among those who died of HIV but did not differ by cause for those who never had AIDS. CONCLUSIONS: The lower prevalence of viral suppression among persons who died of HIV than among those who died of other causes implies a need to improve viral suppression strategies to reduce mortality due to HIV infection.

Telomerase reverse transcriptase promoter mutations in hepatitis B virus-associated hepatocellular carcinoma.

Telomerase reverse transcriptase (TERT) promoter mutations are among the most frequent noncoding somatic mutations in multiple cancers, including hepatocellular carcinoma (HCC). The clinical and pathological implications of TERT promoter mutations in hepatitis B virus (HBV)-associated HCC have not been resolved. To investigate TERT promoter mutations, protein expression, and their clinical-pathological implications, we sequenced the TERT promoter region for hotspot mutations in HCC tissues and performed immunostaining for TERT protein expression from HBV-associated HCC in Chinese patients. Of 276 HCC tumor DNA samples sequenced, 85 (31%) carried TERT promoter mutations. TERT promoter mutations were more frequent in those with low α-fetoprotein (AFP) serum levels (p = 0.03), advanced age (p = 0.04), and in those lacking HCC family history (p = 0.02), but were not correlated with HCC stages and grades. TERT protein levels were higher in HCC (n = 28) compared to normal liver tissues (n = 8) (p =0.001), but did not differ between mutated and non-mutated tumor tissues. In conclusion, TERT promoter mutations are common somatic mutations in HCC of Han Chinese with HBV infection. Detection of TERT promoter mutations in those with low levels of AFP may aid diagnosis of HCC with atypical presentation.

Evaluation and integration of genetic signature for prediction risk of nasopharyngeal carcinoma in Southern China.

UNLABELLED: Genetic factors, as well as environmental factors, play a role in development of nasopharyngeal carcinoma (NPC). A number of single nucleotide polymorphisms (SNPs) have been reported to be associated with NPC. To confirm these genetic associations with NPC, two independent case-control studies from Southern China comprising 1166 NPC cases and 2340 controls were conducted. Seven SNPs in ITGA9 at 3p21.3 and 9 SNPs within the 6p21.3 HLA region were genotyped. To explore the potential clinical application of these genetic markers in NPC, we further evaluate the predictive/diagnostic role of significant SNPs by calculating the area under the curve (AUC). RESULTS: The reported associations between ITGA9 variants and NPC were not replicated. Multiple loci of GABBR1, HLA-F, HLA-A, and HCG9 were statistically significant in both cohorts (P(combined) range from 5.96 × 10(-17) to 0.02). We show for the first time that these factors influence NPC development independent of environmental risk factors. This study also indicated that the SNP alone cannot serve as a predictive/diagnostic marker for NPC. Integrating the most significant SNP with IgA antibodies status to EBV, which is presently used as screening/diagnostic marker for NPC in Chinese populations, did not improve the AUC estimate for diagnosis of NPC.

The principal genetic determinants for nasopharyngeal carcinoma in China involve the HLA class I antigen recognition groove.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA -B, and HLA -C class I genes (P(HLA-A-aa-site-62) = 7.4 × 10(-29); P (HLA-B-aa-site-116) = 6.5 × 10(-19); P (HLA-C-aa-site-156) = 6.8 × 10(-8) respectively). Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9) as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China.

Strong influence of human leukocyte antigen (HLA)-DP gene variants on development of persistent chronic hepatitis B virus carriers in the Han Chinese population.

Chronic hepatitis B virus (HBV) infection is a major health issue, especially in Asia. A recent genome-wide association study (GWAS) implicated genetic variants in the human leukocyte antigen (HLA)-DP locus associated with chronic hepatitis B in Japanese and Thai populations. To confirm whether the polymorphisms at the HLA-DP genes are associated with persistent chronic HBV infection in Han Chinese, we conducted an independent case-control study using 521 persistent chronic HBV carriers and 819 controls that included 571 persons with HBV natural clearance and 248 never HBV-infected (healthy) individuals. Eleven single nucleotide polymorphisms (SNPs) in a region including HLA-DPA and HLA-DPB and an adjacent SNP in strong linkage disequilibrium (LD) with a neighboring HLA-DR13 locus were genotyped using the TaqMan SNP genotyping assay. Eleven variants at HLA-DP showed a strong association with persistent chronic HBV carrier status (P = 1.82 × 10(-12) to 0.01). We also stratified the analysis by HBV clearance status to test the association between these polymorphisms and HBV natural clearance; similar results were obtained (P = 2.70 × 10(-11) to 0.003). Included SNPs define highly structured haplotypes that were also strongly associated with HBV chronic infection (block 1: odds ratio [OR] = 0.54, P = 8.73 × 10(-7) ; block 2: OR = 1.98, P = 1.37 × 10(-10) ). These results further confirm that genetic variants in the HLA-DP locus are strongly associated with persistent HBV infection in the Han Chinese population.

Genetic Polymorphisms of CYP2E1, GSTP1, NQO1 and MPO and the Risk of Nasopharyngeal Carcinoma in a Han Chinese Population of Southern China.

BACKGROUND: Southern China is a major area for endemic nasopharyngeal carcinoma (NPC). Genetic factors as well as environmental factors play a role in development of NPC. To investigate the roles of previously described carcinogen metabolism gene variants for NPC susceptibility in a Han Chinese population, we conducted a case-control study in two independent study population groups afflicted with NPC in Guangdong and Guangxi Provinces of southern China. METHODS: Five single nucleotide polymorphisms (SNPs) of CYP2E1-rs2031920, CYP2E1-rs6413432, GSTP1-rs947894, MPO-rs2333227 and NQO1-rs1800566 were genotyped by PCR-based RFLP, sequencing and TaqMan assay in 358 NPC cases and 629 controls (phase I cohort). Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). To confirm our results, sixteen tag SNPs for GSTP1, MPO, NQO1 (which 100% covered these genes), and 4 functional SNPs of CYP2E1 were genotyped in another cohort of 213 NPC cases and 230 controls (phase II cohort). RESULTS: No significant associations in NPC risk were observed for the five polymorphisms tested in the phase I cohort. In an additional stratified analysis for phase I, there was no significant association between cases and controls in NPC high risk population (EBV/IgA/VCA positive population). Analysis of 14 tagging SNPs within the same genes in an independent phase II cohort were in agreement with no SNPs significantly associated with NPC. CONCLUSIONS: Our results suggest that polymorphism of CYP2E1, GSTP1, MPO and NQO1 genes does not contribute to overall NPC risk in a Han Chinese in southern China.

Evaluation of nonviral risk factors for nasopharyngeal carcinoma in a high-risk population of Southern China.

To understand the role of environmental and genetic influences on nasopharyngeal carcinoma (NPC) in populations at high risk of NPC, we have performed a case-control study in Guangxi Province of Southern China in 2004-2005. NPC cases (n = 1,049) were compared with 785 NPC-free matched controls who were seropositive for IgA antibodies (IgA) to Epstein-Barr virus (EBV) capsid antigen (VCA)-a predictive marker for NPC in Chinese populations. A questionnaire was used to capture exposure and NPC family history data. Risk factors associated with NPC in a multivariant analysis model were the following: (i) a first, second or third degree relative with NPC [attributable risk (AR)= 6%, odds ratio (OR) = 3.1, 95% confidence interval (CI) = 2.0-4.9, p < 0.001]; (ii) consumption of salted fish 3 or more than 3 times per month (AR = 3%, OR = 1.9, 95% CI = 1.1-3.5, p = 0.035); (iii) exposure to domestic wood cooking fires for more than 10 years (AR = 69%, OR = 5.8, 95% CI = 2.5-13.6, p < 0.001); and (iv) exposure to occupational solvents for 10 or less years (AR = 4%, OR = 2.6, 95% CI = 1.4-4.8, p = 0.002). Consumption of preserved meats or a history of tobacco smoking were not associated with NPC (p > 0.05). We also assessed the contribution of EBV/IgA/VCA antibody serostatus to NPC risk-32.2% of NPC can be explained by IgA+ status. However, family history and environmental risk factors cumulatively explained only 2.7% of NPC development in NPC high risk population. These findings should have important public health implications for NPC risk reduction in endemic regions.

GSTM1 and GSTT1 gene deletions and the risk for nasopharyngeal carcinoma in Han Chinese.

Southern China is a major nasopharyngeal carcinoma-endemic region. Environmental factors and genetic susceptibility contribute to nasopharyngeal carcinoma development in this area. Polymorphic deletions of GSTM1 and GSTT1 genes involved in the detoxification of potentially carcinogenic agents may be a risk factor for nasopharyngeal carcinoma. To investigate the roles of genetic variations of GSTM1 and GSTT1 in nasopharyngeal carcinoma susceptibility in the Chinese population, we conducted a case-control study of 350 nasopharyngeal carcinoma cases and 622 controls. GSTM1 and GSTT1 deletion variants were genotyped by multiplex PCR assays. Logistic regression analysis was used to estimate odds ratios and 95% confidence intervals (95% CI). No significant association was observed for either GSTM1- or GSTT1-null genotype independently in the contribution to nasopharyngeal carcinoma risk. To explore possible joint effects of the GSTM1- and GSTT1-null polymorphisms with each other and with other risk factors for nasopharyngeal carcinoma, we examined the association between each combined genotype and the risk for nasopharyngeal carcinoma stratified by gender and EBV replication status. We found that individuals who carried GSTM1/GSTT1-double null genotype had a higher risk for nasopharyngeal carcinoma in the male population (odds ratio, 1.76; 95% confidence interval, 1.04-2.97; P = 0.03); however, this was not significant after correction for multiple comparisons. No statistical difference was found between cases and controls in females and the subpopulation positive for immunoglobulin A antibodies to EBV capsid antigen for combined genotypes. Our results suggest that the GSTM1/GSTT1-double null genotype may be a risk factor for nasopharyngeal carcinoma among males in southern China, but this result warrants confirmation in other studies.

[Association study of chromosome 4 STRs polymorphisms with nasopharyngeal carcinoma].

Nasopharyngeal carcinoma (NPC) is a complex disease caused by an interaction of EBV chronic infection, environment and host genes, in a multi-step process of carcinogenesis. However, which genetic factors play an important role in the development of chronic EBV infection and NPC remain elusive. The objective of this study is to identify genetic variations associated with two key clinical stages of NPC development: persistent Epstein-Barr virus (EBV) infection of nasopharyngeal epithelia and progression to NPC. We inspected a NPC-associated region on the short arm of chromosome 4 previously implicated by a genome-wide linkage analysis of familial NPC. We determined genotypes for 319 alleles in 34 microsatellite markers spanning an 18 Mb region in 350 NPC cases, 288 individuals with IgA antibodies to EBV capsid antigen (IgA/VCA+) and 346 controls seronegative for IgA antibodies to EBV capsid antigen (IgA/VCA-). The cases and controls were Han Chinese from Wuzhou city and Cangwu County, Guangxi province where the incidence of NPC is as high as 25-50 per 100,000 individuals. Comparing NPC cases to IgA/VCA+ subjects, we found 9 alleles marginally associated with developing NPC from IgA+ status, 5 for risk (OR=1.51-5.36, P=0.01-0.03) and 4 for restrictive (OR=0.3-0.71, P=0.02-0.045). Comparing IgA/VCA+ subjects and IgA/VCA- controls, and comparing all IgA seropositives with and without NPC to IgA seronegatives revealed 12 significant and 3 highly significant (P<0.01) alleles associated with IgA+ serostatus in the two comparing groups. Alleles D4S3241-136 (P=0.004, OR=1.91, 95% CI=1.2-3.0) and D4S3347-213 (P=0.001, OR=1.6, 95% CI=1.2-2.1) were for risk. Allele D4S174-202 (P=0.001, OR=0.5, 95%CI=0.3-0.7) was restrictive. However, statistical significance was lost for all when corrected for multiple comparisons test. Our study could not affirm the genetic association within this region with NPC as did another pedigree study, but provide an opportunity for further gene discovery in this highly endemic NPC population and suggest that this region warrants further study.

[Studies on transformation of human esophageal fibroblasts mediated by a retroviral vector containing the E6E7 ORFs of human papillomavirus type 16].

OBJECTIVE: To study the etiological role of human papillomavirus type 16 (HPV16) infection in the development of esophageal cancers. METHODS: A recombinant retrovirus containing the E6E7 ORFs of HPV16 was packaged and human fetal esophageal fibroblasts were infected. The tumorigenecity of the fibroblasts was tested in SCID mice in synergy with 12-O-tetradecanoylphorbol-13-acetate (TPA). RESULTS: Human esophageal fibroblasts infected with the recombinant retrovirus induced sarcomas in SCID mice, the existence and expression of E6E7 ORFs was confirmed in the sarcomas. Fibroblasts cultured from the sarcoma were demonstrated heteroploid by cytoflowmetry. However, tumors were not observed in human fetal esophagus infected with such virus. CONCLUSIONS: These results revealed that the established recombinant retroviral system can successfully mediate the transference of HPV16 E6E7 genes, and such system is applicable to researches on tumorigenesis of HPV.

[Sequence analysis of the deletion and mutation in carboxy terminal region of the Epstein-Barr virus latent membrane protein 1 derived from nasopharyngeal carcinoma patients].

BACKGROUND: To study the deletion and mutation in carboxy terminal region of LMP1 gene derived from nasopharyngeal carcinoma (NPC) in Guangdong and Guangxi, the high risk areas of nasopharyngeal carcinoma in China. METHODS: LMP1 gene carboxy terminal region was amplified from nasopharyngeal carcinoma tissues by PCR, and then cloned and sequenced. RESULTS: Of the 20 cases, 17 were LMP1 positive. In all positive cases, only 1 case did not show deletion. Four positive cases were chosen for DNA sequencing, The rusult showed that all the four cases had mutation and the 30bp deletion. CONCLUSIONS: High frequency of deletion and mutation in LMP1 gene of nasopharyngeal carcinoma tissues was found in Guangdong and Guangxi. Whether it related to the high incidence of NPC should be further studied.

[Detection of Epstein-Barr virus in T cell lymphoma and clinicopathologic analysis].

BACKGROUND: To study the relationship of Epstein-Barr virus (EBV) and T cell lymphoma. METHODS: Sixty cases of T cell lymphomas were examined for the presence of EBV using in situ hybridization for EBV encoded RNA (EBERs). RESULTS: EBERs were detected in tumor cells in 37(69.8%) of 53 cases with peripheral T cell lymphoma, but in none of seven cases of precursor T lymphoblastic lymphoma. The total detected EBERs were 37(61.6%) in 60 cases of T cell lymphomas. By Revised European-American Lymphoma(REAL) classification, EBERs were detected in 2/2 angioimmuno-blastic T cell lymphoma,17/18 angiocentric lymphoma, 4/6 anaplastic large cell lymphoma and 14/27 peripheral T cell lymphoma, unspecified (51.9%). The frequency of EBERs among the extranodal peripheral T cell lymphoma was higher than the nodal (P less than 0.01) there was no significant correlation with the sex, age and clinical stage. CONCLUSIONS: This study indicated that high incidence of EBV was observed in peripheral T cell lymphoma, with predilection for angiocentric lymphoma and extranodal presentation.

[Induction of human cervical carcinoma by human papilloma virus and tumor promoters].

OBJECTIVE: To study the effect of human papillomavirus (HPV) and tumour promoters spermidine (SPD and N-butyrate) on malignant transformation of human embryo cervical cells. METHODS: Plasmid HPV16E6/E7 was constructed and transfected into human embryo cervical cells obtained by induced labor from pregnant women with severe heart diseases. Twenty-one scid mice were divided into 4 groups: experimental group (n = 7, incubated subcutaneously with the transfected cervical cells at the right shoulder, and then injected subcutaneously with spermidine and N-butyrate at the left shoulder three days after the incubation once a week for 12 times), virus-infected group B (n = 5, incubated subcutaneously with transfected cervical cell only), tumor promoter group (n = 5, incubated with untransfected cervical cells and SPD and N-butyrate), and control group (n = 4, incubated subcutaneously with only untransfected cervical cells). Twelve weeks after incubation, the mice were killed. Pathological reexamination was conducted to detect the existence of tumor. PCR was used to detect HPV16E6/E7 gene in tumor tissues. RESULT: Tumor, diagnosed as fibrosarcoma by pathology, was found in 5 out of the 7 mice in the experimental group. The tumor-forming rate was 0 in other groups. Expression of HPV16E6/E7 gene was detected in tumour tissues by PCR. CONCLUSION: HPV16E6/E7 gene containing retrovirus infection, synergized by spermidine and N-butyrate acid, causes malignant transformation in human cervical cells.

[Identification and assessment of multiple human papillomavirus types in condyloma acuminata lesions from patients with genital warts in Beijing area].

OBJECTIVE: To identify and assess multiple human papillomavirus types in condyloma acuminatum lesions from patients with genital warts in Beijing area, and compare different features between otherwise healthy and immunosuppressed patients. METHODS: PCR, RFLP and nucleotide sequencing analysis were used to determine HPV types from individual lesions. RESULTS: The predominant type from other healthy patients was HPV6, secondly HPV11. The mean age of patients infected by HPV6 was lower than that of HPV11 and HPV6 + 11. While lesions from immunosuppressed patients were often contained HPV11 or mixed with HPV6. Besides, HPV types 16 and 53 were detected from infected lesions than other HPV types. CONCLUSIONS: HPV6 was the major pathogen of condyloma acuminatum, but infected patients were at lower ages. While HPV11 was most often detected from immunosuppressed patients. As a low risk virus in normal genital tract, HPV53 also could be a pathogen in genital warts.