Biomedical subjects

Fan Xue

Publications and source records attributed to Fan Xue.

5 recordsLinked to original sources

PubMed2026

Integrative genetic and transcriptomic analyses prioritize CDC16 as a candidate marker for gastric cancer.

BackgroundGastric cancer (GC) remains a major cause of cancer-related mortality, and biomarkers for early detection are needed.MethodsStomach and blood expression quantitative trait loci were integrated with two GC genome-wide association studies using Mendelian randomization (MR), Bayesian colocalization, and summary-data-based MR/heterogeneity in dependent instruments (SMR/HEIDI) testing. Bulk and single-cell transcriptomic analyses characterized candidate expression and lesion-associated patterns. CDC16 protein expression was evaluated by immunohistochemistry in 53 paired GC and non-neoplastic tissues, followed by paired and exploratory receiver operating characteristic analyses.ResultsMR prioritized PILRB, CDC16, and GABPB1-AS1; SMR/HEIDI provided complementary support, while colocalization for CDC16 and GABPB1-AS1 was suggestive and model-dependent. Bulk-tissue CDC16 abundance was higher in GC, but the modest TCGA-STAD tumor-normal difference (log2FC = 0.210, FDR = 0.019) was attenuated after proliferation adjustment (log2FC = -0.002, FDR = 0.987), indicating close coupling with proliferative activity. Single-cell analysis localized CDC16 predominantly to epithelial populations, and the proportion of CDC16-detectable epithelial cells increased across lesion categories (ρ = 0.735; permutation P = 0.031). CDC16 H-scores were higher in GC than in paired non-neoplastic tissues (161.15 ± 45.11 vs 102.15 ± 54.50; P < 0.001), with higher cancer-tissue scores in 41 of 53 cases. Exploratory AUC was 0.794 (95% CI, 0.704-0.874; sensitivity, 66.0%; specificity, 79.2%).ConclusionsConvergent genetic, transcriptomic, and protein-level evidence prioritizes CDC16 as a GC-associated candidate tissue marker whose expression is closely linked to proliferative activity. Prospective validation in independent cohorts, including appropriate disease controls and blood-based evaluation, is warranted.

Stomach Neoplasms↗

PubMed2005

Intrinsic regulation of the interactions between the SH3 domain of p85 subunit of phosphatidylinositol-3 kinase and the protein network of BCR/ABL oncogenic tyrosine kinase.

OBJECTIVE: BCR/ABL fusion tyrosine kinase is responsible for the initiation and maintenance of the Philadelphia chromosome-positive chronic myelogenous leukemia (CML) and a cohort of acute lymphocytic leukemias. We show that a signaling protein, phosphatidylinositol-3 kinase (PI-3k), is essential for growth of CML cells, but not of normal hematopoietic cells, and that p85alpha subunit of PI-3k co-immunoprecipitates with BCR/ABL. Therefore, we made an attempt to better characterize p85alpha-BCR/ABL interactions. MATERIALS AND METHODS: The mutants of p85alpha-SH3 domain were generated by in vitro site-directed mutagenesis system. Protein lysates were obtained from p210BCR/ABL-transformed murine 32Dcl3 myeloid cells, and in vitro transcription/translation was used to produce BCR/ABL protein. Pull-down and Western analyses were performed to detect the interaction between BCR/ABL and p85alpha-SH3. BCR/ABL-transformed 32Dcl3 cells were infected with internal ribosome entry site-green fluorescent protein retroviral construct encoding p85alpha-SH3 mutants to assess their biological effects. RESULTS: We show here that the SH3 domain of p85alpha (p85alpha-SH3) pulls down the p210BCR/ABL kinase from hematopoietic cell lysates. The interaction between p85alpha-SH3 and BCR/ABL may be intermediated by proteins such as c-Cbl, Shc, Grb2, and/or Gab2. Mutations in the p85alpha-SH3 region responsible for proline-rich motif binding either abrogate or enhance these interactions. These mutants exert a modest inhibitory effect on growth factor-independent proliferation of BCR/ABL-positive 32Dcl3 cells. CONCLUSIONS: Based on this information we speculate on the capability of p85alpha-SH3 to interact with the protein network of BCR/ABL oncoprotein.

Amino Acid Substitution↗

PubMed2005

p16 tumor suppressor therapy in salivary adenoid cystic carcinoma cell line SACC83.

OBJECTIVE: This study aimed to determine the growth inhibitory effects of transfecting the wild-type p16 gene into human salivary adenoid cystic carcinoma (SACC) cells in vitro. METHODS: p16 cDNA was cloned into pDOR-neo plasmid by recombination technique, and the human eukaryotic expression vector, pDOR-p16 , was constructed. P16 gene was transfected into SACC83 cells using the liposome method, and the expression of the transfected genes was detected by RT-PCR. The efficacy of transfection was determined by MTT-based colorimetric formats. The DNA metabolic rate of transfected cells was measured by 3 H-TdR incorporation. To describe the cell division phase, the cell cycles of the p16 -transfected gene cells and untransfected cells were analyzed by flow cytometry. RESULTS: The growths in vitro of the p16-transfected cells were inhibited significantly. 3H-TdR incorporation showed a decreased DNA metabolic rate of p16-transfected cells, and flow cytometry suggested a significant increase of the cells in the G1 phase and decrease in the S phase. CONCLUSION: The study confirmed the reversal effect of wild-type p16 on malignant phenotype of the salivary adenoid cystic carcinoma and provides valuable data for further clinical trial of gene therapy with p16.

Carcinoma, Adenoid Cystic↗

PubMed2005

Expression of IgSF in salivary adenoid cystic carcinoma and its relationship with invasion and metastasis.

BACKGROUND: The aim of the present work was to study the potential effect of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and neural cell adhesion molecule (NCAM) of immunoglobulin superfamily on the invasion and metastasis of salivary adenoid cystic carcinoma (SACC). METHOD: The expressions of ICAM-1, VCAM-1 and NCAM of forty cases with SACC were examined by immunohistochemical methods using respective kits. RESULTS: A significant relation showed between the expression level and histological differentiation, expression of ICAM-1 and VCAM-1 in solid SACC was greatly increased compared with NCAM; SACC with metastatic lymph node or local recurrence displayed significant relationship to the up-regulation of ICAM-1 and VCAM-1, and to the down-regulation of NCAM. CONCLUSIONS: It is proposed that ICAM-1 and VCAM-1 may play a role in the invasion and metastasis of SACC. NCAM may be an invasion-resistant adhesion molecule.

Adult↗

PubMed2004

LINKER: a web server to generate peptide sequences with extended conformation.

LINKER was developed as an online server to assist biomedical researchers to design linker sequences for constructing functional fusion proteins. The program automatically generates a set of peptide sequences that are known to adopt extended conformations as determined by X-ray crystallography and NMR. In addition to the desired linker sequence length, the web interface provides a number of optional input parameters so that the users may enhance sequence selection based on the requirements of specific applications. The output of LINKER includes a list of peptide sequences with specified length and sequence characteristics. A graphical subroutine was implemented to highlight the chemical features of every linker sequence by hydrophobicity plots. LINKER can be accessed at http://astro.temple.edu/~feng/Servers/BioinformaticServers.htm.

Amino Acid Sequence↗