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Biomedical subjects

Xiang Guo

Publications and source records attributed to Xiang Guo.

At least 19 recordsLinked to original sources

Induction Paclitaxel-Cisplatin-Capecitabine for Nasopharyngeal Carcinoma.

BACKGROUND: We previously reported higher failure-free survival (FFS) with induction paclitaxel, cisplatin, and capecitabine (TPC) compared with cisplatin and fluorouracil (PF) in high-risk locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We now report 5-year FFS, with prespecified secondary outcomes. METHODS: In this multicenter, randomized trial, patients with high-risk LA-NPC (T4N0-2M0 or TanyN3M0) received two 21-day cycles of induction chemotherapy with TPC or PF, followed by concurrent chemoradiotherapy. The primary endpoint was FFS; secondary endpoints included distant metastasis-free, locoregional relapse-free, and overall survival (OS), tumor response, and safety. RESULTS: Among 238 patients (TPC, n=118; PF, n=120), with median follow-up of 89.1 months, 5-year FFS was 77.6% in the TPC group and 62.9% in the PF group (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.82). At 5 years, distant metastasis-free survival was 87.8% in the TPC group and 78.8% in the PF group (HR, 0.51; 95% CI, 0.28-0.95); locoregional relapse-free survival was 92.0% and 82.1%, respectively (HR, 0.43; 95% CI, 0.21-0.88); and OS was 89.6% and 82.2%, respectively (HR, 0.51; 95% CI, 0.27-0.95). Among patients with pretreatment Epstein-Barr virus (EBV) DNA <3000 copies/ml, 5-year OS was 92.3% in the TPC group and 84.4% in the PF group. Among those with higher EBV DNA levels, rates were 84.2% in TPC group and 81.1% in PF group. Grade 3 or 4 adverse events occurred in 68 patients (57.6%) receiving TPC and 79 patients (65.8%) receiving PF. Treatment adherence was similar in the two groups. CONCLUSIONS: Among patients with high-risk LA-NPC, TPC induction chemotherapy was associated with higher 5-year FFS than PF. (Funded by National Natural Science Foundation of China and State Key Laboratory of Respiratory Disease; ClinicalTrials.gov number, NCT02940925.).

Humans↗

SMART-RNA-Metavirome: a practical RNA metavirome platform compatible with high-throughput sequencing of both short and long reads.

BACKGROUND: The RNA virosphere's extensive diversity and its role in emerging infectious diseases underscore the importance of non-targeted sequencing for identifying unknown or rare pathogens, including co-infections. However, enriching low-abundance viral sequences in RNA metaviromics, particularly in&#xa0;the preparation of cDNA libraries and their compatibility with next-generation sequencing (NGS) and third-generation sequencing (TGS), remains challenging. Therefore, our objective is to develop and systematically assess a practical RNA metavirome methodology specifically tailored for the enrichment of low-abundance viral sequences within samples. METHODS: We developed the SMART-RNA-Metavirome platform, integrating SMART-9n library preparation with NGS and TGS technologies. Total RNA was extracted from two field-collected wild Aedes albopictus pools, along with one laboratory-infected Ae. albopictus pool harboring dengue virus (DENV). This RNA was subjected to reverse transcription using both this optimized protocol and random primer-based methods, followed by high-throughput sequencing on Illumina, Oxford Nanopore, and QitanTech Nanopore technologies. Welch's t-test was employed for comparative analysis of the subsequent RNA metavirome data, specifically to evaluate differences in viral species composition and abundance of viral reads between experimental groups. Furthermore, the effectiveness of this platform was systematically validated via RT-qPCR and SMART-RNA-Metavirome-based Oxford&#xa0;Nanopore sequencing across multiple sample types, including mosquito specimens from DENV-infected Ae. albopictus, serum samples from dengue patients and viral isolates of Japanese encephalitis virus (JEV) and Zika virus (ZIKV). RESULTS: The SMART-RNA-Metavirome platform has been systematically validated to excel in enriching the composition and diversity of the RNA virome (P&#x2009;=&#x2009;0.04), providing sufficient coverage for the complete reconstruction of viral genomes. When employed in the detection of DENV-infected Ae. albopictus, clinical serum samples, and viral isolates of JEV and ZIKV, this technique exhibits a robust correlation with RT-qPCR (r2&#x2009;>&#x2009;0.95). Notably, it demonstrates exceptional sensitivity, ensuring sufficient coverage even in samples of DENV-infected Ae. albopictus with a Ct-value of 35.3, attaining an impressive 99.88% genome coverage. Furthermore, this platform possesses the capability to identify virus species and determine their serotypes. CONCLUSIONS: In our study, the SMART-RNA-Metavirome platform outperforms traditional methods, enriching RNA virome composition and diversity, enabling practical compatibility with both NGS and TGS technologies. It demonstrates significant proficiency in detecting both known and unknown arboviruses, even in low-titer samples such as those from wild mosquitoes and clinical sera. This platform facilitates comprehensive monitoring, risk assessment, and early warning of RNA virus transmissions, enhancing our understanding of RNA virome diversity and ecological patterns.

High-Throughput Nucleotide Sequencing↗

Therapeutic targeting of the endothelin a receptor in human nasopharyngeal carcinoma.

The endothelin A receptor (ET(A)R) autocrine pathway is overexpressed in many malignancies, including nasopharyngeal carcinoma (NPC). In this tumor, ET(A)R expression is an independent determinant of survival and a robust independent predictor of distant metastasis. To evaluate whether ET(A)R represents a new target in NPC treatment, we tested the therapeutic role of ET(A)R in NPC. Cell proliferation was inhibited by the ET(A)R-selective antagonist ABT-627 in two ET(A)R-positive NPC cells in a dose-dependent manner. Proliferation of ET(A)R-negative NPC cells was not decreased. ET(A)R blockade also resulted in sensitization to cisplatin and 5-fluorouracil-induced apoptosis. In nude mice, ABT-627 inhibited the growth of NPC cell xenografts. Combined treatment of ABT-627 with the cytotoxic drug cisplatin or 5-fluorouracil produced additive antitumor effects. The antitumor activity of ABT-627 was demonstrated finally on an experimental lung metastasis by a reduction in the number of tumors. These results support the rationale of combining ABT-627 with current standard chemotherapy to further improve the therapeutic ratio in the treatment of NPC.

Animals↗

Elevated plasma big ET-1 is associated with distant failure in patients with advanced-stage nasopharyngeal carcinoma.

BACKGROUND: Endothelin-1 (ET-1) is a potent vasoactive peptide and a hypoxia-inducible angiogenic growth factor associated with the development and spread of solid tumors. The clinical significance of plasma big ET-1 in patients with advanced-stage nasopharyngeal carcinoma (NPC) is not known. METHODS: Pretreatment plasma big ET-1 levels were measured in 62 patients with advanced-stage NPC using a sandwich enzyme-linked immunoassay and compared with the levels from a control group (n = 19 participants). RESULTS: The median pretreatment plasma big ET-1 level in patients with advanced-stage NPC was 4.6 pg/mL (range, 1.9-15.2 pg/mL) and was significantly elevated compared with median plasma big ET-1 levels in healthy controls, 2.6 pg/mL (1.6-4.5 pg/mL) (P < .001). Using the upper limit (4.5 pg/mL) of control subjects as the cut-off value, plasma big ET-1 was < or = 4.5 pg/mL in 29 (46.8%) patients and > 4.5 pg/mL in 33 (53.2%) patients. A pretreatment plasma big ET-1 level > 4.5 pg/mL was associated with a significantly poorer 2-year distant metastasis-free survival rate (56.7% vs. 81.1%, P = .031). Multivariate analysis showed that N classification (hazard ratio [HR], 2.416; 95% confidence interval [CI], 1.071-5.447; P = .034) and pretreatment plasma big ET-1 level (HR, 3.151; 95% CI, 1.099-9.028, P = .033) were independent significant prognostic factors for posttreatment distant failure in patients with advanced-stage NPC. CONCLUSIONS: Pretreatment plasma big ET-1 levels may be useful in predicting posttreatment distant failure in patients with advanced-stage NPC.

Adult↗

Assessing semantic similarity measures for the characterization of human regulatory pathways.

MOTIVATION: Pathway modeling requires the integration of multiple data including prior knowledge. In this study, we quantitatively assess the application of Gene Ontology (GO)-derived similarity measures for the characterization of direct and indirect interactions within human regulatory pathways. The characterization would help the integration of prior pathway knowledge for the modeling. RESULTS: Our analysis indicates information content-based measures outperform graph structure-based measures for stratifying protein interactions. Measures in terms of GO biological process and molecular function annotations can be used alone or together for the validation of protein interactions involved in the pathways. However, GO cellular component-derived measures may not have the ability to separate true positives from noise. Furthermore, we demonstrate that the functional similarity of proteins within known regulatory pathways decays rapidly as the path length between two proteins increases. Several logistic regression models are built to estimate the confidence of both direct and indirect interactions within a pathway, which may be used to score putative pathways inferred from a scaffold of molecular interactions.

Databases, Protein↗

Prognostic value of Survivin and Livin in nasopharyngeal carcinoma.

BACKGROUND AND OBJECTIVES: Survivin and Livin are new members from the family of anti-apoptotic factors. Increased levels of Survivin and Livin have been observed in many malignancies and correlated with poor prognosis. Survivin is expressed almost exclusively in proliferating cells, including various kinds of cancers, but Livin expression is relatively rare in cancer cells. Therefore, the present study examines the expressions of Survivin and Livin in nasopharyngeal carcinoma (NPC) and investigates whether their expression contributes to the prognosis of NPC. METHODS: We investigated the expression of Survivin and Livin in 80 NPC samples using immunohistochemistry stain and correlated it with the survival of these patients using log-rank test and Cox multifactor regression analysis. RESULTS: All the patients were followed up at least for 60 months. During the following period, 21 cases developed distant metastasis, 9 cases developed local-regional recurrence, and 5 developed both distant metastasis and local-regional recurrence. Among them, 30 patients died of recurrence of tumor. In addition, the expression of Survivin was related with distant metastasis. Patients with low Survivin expression had better overall survival, disease-free survival and distant metastasis-free survival rates than the group with high Survivin expression (P = .0086, .0097, and .0318, respectively). Cox regression analysis confirmed that high Survivin expression was related to worse prognosis in NPC patients. However Livin expression level was not related with the survival of patients with NPC. CONCLUSION: NPC expresses high levels of Survivin and Livin, which may play an important role in the oncogenesis and tumor development. Over-expression of Survivin was related with poor prognosis. We suggest that the determination of Survivin expression may provide predictive information on NPC patients.

Adaptor Proteins, Signal Transducing↗

[Clinical analysis of 1,142 hospitalized cantonese patients with nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Few large-scale epidemiologic investigations of nasopharyngeal carcinoma (NPC) at high incidence region in Guangdong province were reported in recent 20 years. This study was to summarize clinical data of a population of hospitalized Cantonese NPC patients,analyze the epidemiologic characteristics of NPC in the high incidence region, and provide references for the prevention and treatment of NPC. METHODS: Clinical data of 1 142 Cantonese NPC patients, hospitalized in Cancer Center of Sun Yat-sen University between Jan. 1998 and Aug. 2000, were collected according to well-designed forms and statistically analyzed. RESULTS: The morbidity of NPC in Cantonese showed obvious family clustering: 21.9% of the patients had family history of cancer, and 12.3% had family history of NPC. Moreover, the family clustering feature was more obvious in the population from the region with higher incidence of NPC. The positive rate of VCA/IgA antibody was 90.0%, and that of EA/IgA antibody was 74.5%; the titers were positively related to tumor burden. Early diagnostic rate of NPC was about 30%. CONCLUSIONS: NPC patients in Cantonese population have obvious family and territorial clustering. High positive rates of VCA/IgA and EA/IgA antibodies are helpful for early diagnosis of NPC.

Adolescent↗

[Induction of apoptosis and inhibition of HL-60 cell proliferation by survivin antisense oligonucleotide].

OBJECTIVE: To investigate the effects of survivin antisense oligonucleotide (ODN) on cell proliferation and apoptosis of HL-60 cells. METHODS: Synthetic ODN was completely phosphorothioate-modified. Cationic lipid-mediated antisense ODN was transferred into HL-60 cells. The expression of survivin mRNA and protein was detected by RT-PCR and Western Blot. The incorporation of MTT was used as the measurement of HL-60 proliferation. The cell-cycle and apoptosis were analyzed by flow cytometry. RESULTS: HL-60 cells spontaneously expressed survivin mRNA and protein. Both mRNA and protein expression of survivin decreased significantly in the antisense ODN transfected cells in comparison to that in the original cells and cells transfected with sense ODN. Survivin antisense ODN significantly inhibited cell proliferation and induced apoptosis in a dose-dependent manner. The cell-cycle in the antisense ODN-transfected cells stopped at the G2/M phase. CONCLUSIONS: Antisense ODN targeting at survivin mRNA can inhibit HL-60 cell proliferation and induce G2/M stop and apoptosis.

Apoptosis↗

Histone acetylation and transcriptional regulation in the genome of Saccharomyces cerevisiae.

MOTIVATION: In eukaryotic genomes, histone acetylation and thereafter departure from the chromatin are essential for gene transcription initiation. Because gene transcription is tightly regulated by transcription factors, there are some speculations on the cooperation of histone acetylation and transcription factor binding. However, systematic statistical analyses of this relationship on a genomic scale have not been reported. RESULTS: We apply several statistical methods to explore this relationship on two recent genomic datasets: acetylation levels on 11 histone lysines and binding activities of 203 transcription factors, both in promoter regions across the yeast genome. By canonical correlation analysis, we find that a histone acetylation pattern is correlated with a certain profile of transcription factor binding in the genome. Furthermore, after clustering the genes by their acetylation levels on the 11 histone lysines, the genes within clusters show distinct transcription factor binding profiles, as discovered by principle component analysis. Even after applying fairly stringent statistical measurement, most of these clusters have transcription factors with binding activities significantly deviated from the overall genome. We conclude that in the yeast genome, there is a strong correlation between histone acetylation and transcription factor binding in the promoter regions.

Acetylation↗

[Correlation of endothelin A receptor expression to prognosis of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Endothelin A receptor (ET(A)R) activation contributes to tumor growth and metastasis, including cell proliferation, cell death, angiogenesis, and metastatic spread. In this study, we evaluated correlation of ET(A)R expression to clinical features of nasopharyngeal carcinoma (NPC), and explored its correlation to prognosis. METHODS: Expression of ET(A)R in 153 specimens of NPC was detected by SABC immunohistochemistry. RESULTS: Positive rate of ET(A)R was 73.9% in the 153 NPC specimens. No correlation was found between ET(A)R expression and gender, age, T stage, N stage, and TNM stage of the patients. The 3-year overall survival rate, relapse-free survival rate, and distant metastasis-free survival rate were significantly higher in ET(A)R-negative patients than in ET(AR-positive patients (87.5% vs. 73.2%, P = 0.029; 80.0% vs. 57.3%, P = 0.009; and 89.9% vs. 70.4%, P = 0.012), except for local relapse-free survival rate (86.9% vs. 80.2%, P = 0.228). Cox multivariate analysis showed that ET(A)R expression, gender, age, T stage, and N stage were independent prognostic factors, which affected overall survival, relapse-free survival, and distant metastasis. CONCLUSION: ET(A)R expression is an important distant metastasis-related risk factor for patients with NPC; its overexpression indicates poor prognosis.

Adolescent↗

[Impact of pre-radiotherapy hemoglobin level on local control of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Oxygen increases tumor sensitivity to radiotherapy; tumor hypoxia is more prevalent in tumor patients with pretreatment hemoglobin concentration of < 130 g/L. This study was to evaluate impact of pre-radiotherapy hemoglobin level on radiotherapy outcome of nasopharyngeal carcinoma (NPC) patients. METHODS: Clinical and follow-up data of 166 NPC patients received definitive radiotherapy from 1999 to 2000 were reviewed. Pre-radiotherapy hemoglobin levels were stratified as high (> or =130 g/L) and low (< 130 g/L). Cox regression analysis was used to determine factors affecting local control. RESULTS: The median pre-radiotherapy hemoglobin level of the 166 patients was 135 (85-189) g/L. Hemoglobin was < 130 g/L in 68 (41%) patients, and > or =130 g/L in 98 (59%) patients. The pre-radiotherapy hemoglobin level of < 130 g/L was related to low 3-year local relapse-free survival rate (78% vs. 90%, P=0.015), but had no relations with distant metastasis-free survival (75% vs.77%, P=0.763) and overall survival rates (73% vs. 83%, P=0.056). Multivariate analysis showed that pre-radiotherapy hemoglobin level, T stage, and gender were independent prognostic factors for local failure. CONCLUSIONS: Pre-radiotherapy hemoglobin of < 130 g/L is a prognostic factor for local control of NPC. Strategies for maintaining pre-radiotherapy hemoglobin of > or =130 g/L before radiotherapy and during treatment should be further explored.

Adolescent↗

[Effect of warming needle moxibustion on pain threshold in the patient of sciatica].

OBJECTIVE: To observe effect of warming needle moxibustion on pain threshold in the patient of sciatica. METHODS: Ninety cases were randomly divided into 3 groups, 30 cases in each group. The warming needle moxibustion group were treated with warming needle moxibustion at Shenshu (BL 23), Dachangshu (BL 25), Huantiao (GB 30), etc; the western medicine group with oral administration of Nimeisulide; and the acupoint-injection group with injection of 654-2 into the same acupoints as those in the warming needle moxibustion group. RESULTS: The cured rates were 56.67%, 26.67% and 20.00% in the 3 groups, and the total effective rate were 90.00%, 73.33% and 63.33%, respectively, the therapeutic effect of the warming needle moxibustion group being better than those of other two groups (both P < 0.01). The amplitude of pain threshold increase in the warming needle moxibustion group was higher than those of other two groups (both P < 0.01). CONCLUSION: Warming needle moxibustion can increase pain threshold, improve symptoms and raise quality of life for the patient of sciatica.

Humans↗

[Surgery for the recurrent and persistent lymph node of nasopharyngeal carcinoma after radiotherapy].

OBJECTIVES: To investigate the effect of four types of neck dissections for the recurrent and persistent lymph nodes of NPC after radiotherapy. METHODS: The clinical data of 88 cases of nasopharyngeal carcinoma with recurrent and persistent lymph nodes after radiotherapy were analyzed retrospectively, the 5-year survival rate, recurrent rate, distant metastatic rate and surgical complications were analyzed. The survival rate and recurrent rate of the radical neck dissection (RND), modified radical neck dissection (MRND), selective neck dissection (SND) and lymph node resection (LNR) were compared. The survival and recurrent rate between those with and without postoperative radiotherapy were investigated as well. RESULTS: The 5-year survival rate and recurrent rate of whole group were 42.8% and 22.7%, respectively. As for the patients with disease staged II, III, IV, the 5-year survival rates were 56.7%, 36.1% and 32.4%, respectively. The 5-year survival rate of groups of RND, MRND, SND and LMR were 39.8%, 60.0%, 37.9% and 44.1%, respectively, the differences were insignificant (Log Rank = 1.0, P = 0.8011), the recurrent rate of the lymph node among the 4 groups were insignificant either (chi2 = 0.470, P = 0.493). The 5-year survival rates of those with and without postoperative radiotherapy were 39.1% and 45.3%, respectively, the differences were insignificant (Log Rank = 0.06, P = 0.8138), the recurrent rate of the two groups were insignificant (chi2 = 0.593, P = 0.441). CONCLUSIONS: The four types of neck dissection were effective and safe to control the recurrent and persistent lymph nodes in the neck after radiotherapy, as long as choosing patients rationally and gave postoperative radiotherapy if necessary.

Adult↗

Genetic and expression profiles of squamous cell carcinoma of the head and neck correlate with cisplatin sensitivity and resistance in cell lines and patients.

PURPOSE: The choice of treatment for squamous cell carcinoma of the head and neck (SCCHN) is still primarily based on the tumor-node-metastasis classification. However, it is reasonable to believe that biological profiles of SCCHN may be independently associated with response to therapy. The aim of the present study was to examine genetic changes and gene expression profiles that might correlate with sensitivity to cisplatin [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] in 10 SCCHN cell lines. EXPERIMENTAL DESIGN: Five cisplatin-sensitive and five cisplatin-resistant cell lines [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] were studied by comparative genomic hybridization, spectral karyotyping, and cDNA microarray analysis (21,632 sequence-validated human cDNA; confirmation by reverse transcriptase-PCR for selected genes). For the MET proto-oncogene, which showed low expression in the chemosensitive cell lines, we did immunohistochemical staining on SCCHN of 29 patients who received induction chemotherapy. RESULTS: The five cisplatin-resistant cell lines showed significantly more genetic imbalances (regions of loss and amplification) and chromosomal abnormalities by comparative genomic hybridization and spectral karyotyping, respectively, than did the five cisplatin-sensitive cell lines. Microarray studies identified approximately 60 genes that clearly distinguish between the two groups of cell lines. Some of these genes are known to be involved in tumor progression, metastasis, and drug resistance. We identified low expression of c-met (immunohistochemistry) as a predictive factor for complete response in nondiploid tumors (P = 0.026). CONCLUSIONS: We conclude that cisplatin sensitivity and resistance are related to distinctive differences in the genetic and expression profiles in individual SCCHN tumor cell lines and in SCCHN patients. The genes we have identified may serve as potential targets for novel treatment strategies.

Adult↗

High frequency of common deletion (4981 bp) in mitochondrial DNA in nasopharyngeal carcinoma and its correlation with patient age and clinical stages.

Mitochondrial DNA (mtDNA) has a high mutation rate due at least in part to a lack of protective histones and an inefficient DNA repair system. The most frequently change in mtDNA is the so-called Common Deletion (CD), which accumulates in patients with heteroplasmic mtDNA mutations and in normal individuals during aging. In this study, wild type mtDNA (WT-mtDNA) and mitochondrial DNA with CD (CD-mtDNA) were quantitatively analyzed in different nasopharynx lesions. A novel type of CD-mtDNA (4981 bp) was detected significantly higher in nasopharyngeal carcinoma (NPC) (93%, 54/58) than in nasopharyngitis (60%, 28/47) and the paired white blood cells (WBC) (26%, 8/31). The ratio of CD-mtDNA to WT-mtDNA in NPC (0.000625, median) was ten times that in nasopharyngitis (0.000064, median) (P=0.003), and was significantly higher than that in paired WBC (0.000000, median) (P=0.000). The CD/WT-mtDNA ratio was 0.000564 (quartile range, 0.000184-0.000919) in late stage NPC, which was nearly three times the ratio in early stage NPC (0.000164, quartile range, 0.000042-0.000353) (P=0.015, Mann-Whitney Test). In NPC patients with ages <48yrs (mean age), the ratio of CD-mtDNA to WT-mtDNA was 0.000625, which was nearly ten times that in NPC patients with ages<48yrs (0.000064) (P=0.005, Mann-Whitney Test). This is the first quantitative study of CD-mtDNA mutations in NPC, which provides evidences that CD-mtDNA mutation might be involved in the development and progression of NPC.

Adult↗