Biomedical subjects

Xiaojuan Wang

Publications and source records attributed to Xiaojuan Wang.

16 recordsLinked to original sources

PubMed2026

SYT8 Drives Colorectal Cancer Progression and Immune Evasion via the SETD1A-H3K4me3 Axis.

By integrating transcriptomic data from The Cancer Genome Atlas, Gene Expression Omnibus, and a self-established colorectal cancer (CRC) cohort, it was identified that synaptotagmin 8 (SYT8) is significantly up-regulated in tumors and is predictive of poor prognosis. Single-cell RNA sequencing, immunohistochemistry, and immunofluorescence experiments demonstrate that SYT8 expression is largely confined to tumor cells, predominantly in the nucleus. Functional assays reveal that depletion of SYT8 impairs, whereas its overexpression enhances, CRC cell proliferation and invasion. Transcriptomic profiling indicates an enrichment of cell cycle and epithelial-mesenchymal transition signatures. Mechanistically, co-immunoprecipitation/mass spectrometry identifies SET domain containing 1A (SETD1A) as a direct SYT8-interacting partner. The SYT8-SETD1A axis forms a positive-feedback loop that increases histone H3 lysine 4 trimethylation (H3K4me3) levels and drives the transcription of protumorigenic genes. Immune profiling further indicates that high SYT8 expression correlates with increased regulatory T-cell infiltration, suggesting an immunosuppressive microenvironment and potential resistance to immunotherapy. Collectively, SYT8 promotes CRC progression through the SETD1A/H3K4me3-mediated activation of the cell cycle, induction of epithelial-mesenchymal transition, and remodeling of the immune microenvironment. Therefore, SYT8 is established as a prognostic biomarker and serves as a therapeutic target in colorectal cancer.

Humans↗

PubMed2006

Myoepithelial carcinoma arising in an adenomyoepithelioma of the breast: case report with immunohistochemical and mutational analysis.

Adenomyoepithelioma (AME) of the breast is an uncommon tumor characterized by biphasic proliferation of both epithelial and myoepithelial cells. In rare instances, the epithelial, the myoepithelial or both components of an AME may become malignant. Described herein is the case of a 69-year-old woman who presented with myoepithelial carcinoma of the breast in an AME. Malignancy of myoepithelial component (MEC) was evidenced by the presence of cytological atypia, high mitotic rate, necrosis and local invasion. Immunohistochemical study demonstrated strong expression of P53 and phosphorylated extracellular signal-regulated kinase 1/2 in MEC. Laser capture microdissection technique and mutational analysis further revealed point mutation of the p53 gene (T-->G transversion at codon 270) in this population, but not in glandular epithelial cells or adjacent normal ductal epithelium. No mutations in exons 1 and 2 of the K-, H-, and N-ras genes were identified in any of the neoplastic component. To the authors' knowledge this is the first report of a mutation in the p53 gene in a malignant AME of the breast.

Aged↗

PubMed2005

Effect of aging on neuroglobin expression in rodent brain.

Neuroglobin (Ngb), a recently discovered O2-binding heme protein related to hemoglobin and myoglobin, protects neurons from hypoxic-ischemic injury in vitro and in vivo. In immunostained mouse brain sections, we found widespread expression of Ngb protein in neurons, but not astrocytes, of several brain regions that are prominently involved in age-related neurodegenerative disorders. Western blots from young adult (3 month), middle-aged (12 month), and aged (24 month) rats showed an age-related decline in Ngb expression in cerebral neocortex, hippocampus, caudate-putamen, and cerebellum. Loss of this neuroprotective protein may have a role in increasing susceptibility to age-related neurological disorders.

Age Factors↗

PubMed2005

Combined small-cell carcinoma of the stomach: p53 and K-ras gene mutational analysis supports a monoclonal origin of three histological components.

Primary small-cell carcinoma (SmCC) is extremely rare in stomach. We reported an autopsy case of combined gastric SmCC with p53 and K-ras mutational analysis. Histologically, the tumour was composed of well-differentiated adenocarcinoma surrounding the central dominant SmCC component with scattered nests of squamous cell carcinoma. Immunohistochemically, all the neoplastic components revealed strong expression for p53 protein. Based on these findings, we hypothesized that these histologically different components originated from a same progenitor cell that possessed p53 mutation. Using Laser-capture microdissection technique and mutational analysis, we identified the same point mutations of p53 gene (A-->G transversion in codon 239) and K-ras gene (G-->A transversion in codon 13) in all the neoplastic components, but not in the adjacent normal gastric epithelium. Our results strongly support a hypothesis that the combined SmCC of stomach in this case was of monoclonal origin.

Adenocarcinoma↗

PubMed2004

Kinetics of end-to-end collision in short single-stranded nucleic acids.

A novel fluorescence-based method, which entails contact quenching of the long-lived fluorescent state of 2,3-diazabicyclo[2.2.2]-oct-2-ene (DBO), was employed to measure the kinetics of end-to-end collision in short single-stranded oligodeoxyribonucleotides of the type 5'-DBO-(X)n-dG with X = dA, dC, dT, or dU and n = 2 or 4. The fluorophore was covalently attached to the 5' end and dG was introduced as an efficient intrinsic quencher at the 3' terminus. The end-to-end collision rates, which can be directly related to the efficiency of intramolecular fluorescence quenching, ranged from 0.1 to 9.0 x 10(6) s(-1). They were strongly dependent on the strand length, the base sequence, as well as the temperature. Oligonucleotides containing dA in the backbone displayed much slower collision rates and significantly higher positive activation energies than strands composed of pyrimidine bases, suggesting a higher intrinsic rigidity of oligoadenylate. Comparison of the measured collision rates in short single-stranded oligodeoxyribonucleotides with the previously reported kinetics of hairpin formation indicates that the intramolecular collision is significantly faster than the nucleation step of hairpin closing. This is consistent with the configurational diffusion model suggested by Ansari et al. (Ansari, A.; Kuznetsov, S. V.; Shen, Y. Proc.Natl. Acad. Sci. USA 2001, 98, 7771-7776), in which the formation of misfolded loops is thought to slow hairpin formation.

Bridged Bicyclo Compounds, Heterocyclic↗

PubMed2004

Calcitonin receptor gene and breast cancer: quantitative analysis with laser capture microdissection.

There is a growing body of evidence indicating that calcitonin (CT) and its receptor (CTR) is involved in cell growth, differentiation and tissue development. Using laser capture microdissection (LCM) and real-time reverse transcription polymerase chain reactions (RT-PCR), we have investigated CTR mRNA expression in 60 primary breast cancers, including 14 pairs of matched cancers and unaffected ductal epithelia from the same patients. Our results demonstrate that CTR mRNA was constantly expressed in normal ductal epithelium and in breast cancer. In the 14 cases where matched samples were available, a decrease in CTR mRNA expression was found in 9 breast cancers (64.3%), an increased CTR expression in 2 cases (14.3%) and no significant change in 3 cases (21.4%). In 60 cases of primary breast cancers, decreased CTR expression was found in 44 (73.3%), increased CTR expression was detected in 10 cases (16.7%) and no change was observed in 6 cases (10%). Decreased CTR expression was found more often in cases with lymph node metastasis (p = 0.0498) and lymphatic invasion (p = 0.0179). Also there was a decreased CTR expression in cases with an extensive intraductal component (p = 0.0543) and a high nuclear grade (p = 0.1934), although this was not statistically significant. Overall, we conclude that CTR mRNA was constantly expressed in unaffected ductal epithelium, whereas decreased CTR mRNA expression was frequently found in breast cancers, particularly in cases with lymph node metastasis and lymphatic invasion. These results suggest that CTR might be of great potential significance in breast cancer progression.

Adult↗

PubMed2004

Effect of arsenic trioxide (ATO) on human lung carcinoma PG cell line: ATO induced apoptosis of PG cells and decreased expression of Bcl-2, Pgp.

Arsenic trioxide (ATO) has been established to be an effective agent for treating newly diagnosed and relapsed acute promyelocytic leukemia (APL) patients. Laboratory data suggest that ATO induces apoptosis of hematopoietic or several solid tumor cells. However, to date, its effect on lung carcinoma has not been fully explored. In the present study, we investigated the effect of ATO on human lung carcinoma PG cells in vitro. We found ATO significantly inhibited the proliferation of PG cells in a dose- and time-dependent manner. ATO-induced apoptosis of PG cells was confirmed by the observance of typical morphological changes and detected by the analysis of flow cytometry (FCM). ATO significantly inhibited Bcl-2 and Pgp expression of PG cells by SABC immunohistochemistry and FCM analysis. In conclusion, our findings indicated that ATO induced apoptosis of PG cells and down-regulation of Bcl-2 and Pgp expressions, and these data might provide some theoretical basis for its clinical use in treating lung carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Differentiation, proliferation and retinoid receptor status of papillary carcinoma of the thyroid.

Messenger RNA expression of retinoic acid receptors (RARalpha, RARbeta and RARgamma) and retinoid X receptors (RXRalpha, RXRbeta and RXRgamma) was examined using reverse transcription-polymerase chain reaction in 42 papillary thyroid carcinomas (PTCs). A loss of mRNA expression was observed in 18 cases of the 42 PTCs, including three cases for RARalpha, 14 cases for RARbeta, six cases for RXRalpha and five cases for RXRbeta. The expressions of RARgamma and RXRgamma were found in all 42 PTCs. Based on Ki 67/MIB1 labeling index (LI), the 42 PTCs were classified into Group A (20 cases; LI = 0-2%), Group B (17 cases; LI = 2-5%) and Group C (5 cases; LI > 5%). The PTCs of groups B and C showed solid, trabecular or scirrhous arrangements, infiltrative growth, loss of cellular polarity and cohesiveness more frequently, but capsulated growth pattern less frequently, when compared with PTCs of Group A. They also showed more frequent extrathyroidal extension than Group A. However, no significant differences were identified in sex, age, nodal status and tumor size. Loss of expression for one or more retinoid receptors frequently occurred in groups B and C. These results suggest that the loss of retinoid receptors might occur during the loss of differentiation and tumor progression of PTC.

Adult↗

PubMed2002

A pantothenate auxotroph of Mycobacterium tuberculosis is highly attenuated and protects mice against tuberculosis.

With the advent of HIV and the widespread emergence of drug-resistant strains of Mycobacterium tuberculosis, newer control strategies in the form of a better vaccine could decrease the global incidence of tuberculosis. A desirable trait in an effective live attenuated vaccine strain is an ability to persist within the host in a limited fashion in order to produce important protective antigens in vivo. Attenuated M. tuberculosis vaccine candidates have been constructed by deleting genes required for growth in mice. These candidate vaccines did not elicit adequate protective immunity in animal models, due to their inability to persist sufficiently long within the host tissues. Here we report that an auxotrophic mutant of M. tuberculosis defective in the de novo biosynthesis of pantothenic acid (vitamin B5) is highly attenuated in immunocompromised SCID mice and in immunocompetent BALB/c mice. SCID mice infected with the pantothenate auxotroph survived significantly longer (250 days) than mice infected with either bacille Calmette-Guerin (BCG) vaccine or virulent M. tuberculosis (77 and 35 days, respectively). Subcutaneous immunization with this auxotroph conferred protection in C57BL/6J mice against an aerosol challenge with virulent M. tuberculosis, which was comparable with that afforded by BCG vaccination. Our findings highlight the importance of de novo pantothenate biosynthesis in limiting the intracellular survival and pathogenesis of M. tuberculosis without reducing its immunogenicity in vaccinated mice.

Animals↗

PubMed2002

Biomolecular and supramolecular kinetics in the submicrosecond time range: the fluorazophore approach.

Fluorophores based on the azo chromophore 2,3-diazabicyclo[2.2.2]oct-2-ene, referred to as fluorazophores, display an exceedingly long fluorescence lifetime and undergo quenching upon contact with efficient hydrogen or electron donors. These photophysical and photochemical properties allow several uncommon applications to biomolecular and supramolecular kinetic studies in the submicrosecond time range. Examples for kinetics of host-guest complexation, end-to-end contact formation in polypeptides, and lateral diffusion in membrane models are described. Principal requirements for these types of kinetic measurements and the dependence of the kinetics of diffusion-controlled reactions on the dimensionality of the system are discussed.

Bridged Bicyclo Compounds, Heterocyclic↗

PubMed2002

A joint structural, kinetic, and thermodynamic investigation of substituent effects on host-guest complexation of bicyclic azoalkanes by beta-cyclodextrin.

Derivatives of the azoalkane 2,3-diazabicyclo[2,2,2]oct-2-ene (1a) with bridgehead 1,4-dialkyl (1b), 1,4-dichloro (1c), 1-hydroxymethyl (1d), 1-aminomethyl (1e), and 1-ammoniummethyl (1f) substituents form host-guest inclusion complexes with beta-cyclodextrin. They were employed as probes to assess substituent effects on the kinetics and thermodynamics of this complexation by using time-resolved and steady-state fluorimetry, UV spectrophotometry, induced circular dichroism (ICD) measurements, and (1)H NMR spectroscopy. The kinetic analysis based on quenching of the long-lived fluorescence of the azoalkanes by addition of host provided excited-state association rate constants between 2.6 x 10(8) and 7.0 x 10(8) M(-)(1) s(-)(1). The binding constants for 1a (1100 M(-1)), 1b (900 M(-1)), 1c (1900 M(-1)), 1d (180 M(-1)), 1e (250 M(-1)), and 1f (ca. 20 M(-1)) were obtained by UV, NMR, and ICD titrations. A positive ICD signal of the azo absorption around 370 nm was observed for the beta-cyclodextrin complexes of 1a, 1d, and 1f with the intensity order 1a >> 1d approximately 1f, and a negative signal was measured for those of 1b, 1c, and 1e with the intensity order 1c < 1b approximately 1e. The ICD was employed for the assignment of the solution structures of the complexes, in particular the relative orientation of the guest in the host (co-conformation).

Azo Compounds↗

PubMed2002

Gastrointestinal stromal tumors: are they of cajal cell origin?

Recently some reports have suggested that gastrointestinal stromal tumors (GIST) might originate from the interstitial cells of Cajal or differentiate into them because they express c-kit and/or CD34 and indicated that the majority of previously diagnosed smooth muscle tumors (SMT) actually belong to GIST, but are not true SMT. We, therefore, detected c-kit, CD34, SMA, and S-100 in 106 Chinese cases of gastrointestinal tumors, which were histopathologically diagnosed as smooth muscle tumors originally, to demonstrate the immunophenotypes of these tumors. The results showed that 73 cases had immunoreaction with c-kit and/or CD34, of which 48 cases showed coexpression with either SMA or S-100 or with both. A correlation between the immunophenotypes and known histopathological parameters was also shown here based on follow-up data. We suggest that the concept of GIST should not be used as an umbrella to cover all gastrointestinal mesenchymal tumors, but be defined in a narrow term as differing from true smooth muscle tumors.

Actins↗

PubMed2002

p63 expression in normal, hyperplastic and malignant breast tissues.

BACKGROUND: p63 is a homologue of the p53 tumor suppressor gene and its protein is selectively expressed in the basal cells of a variety of epithelial tissues. It has recently been confirmed that p63 is expressed in the basal cells of normal prostate glands but not in prostatic carcinomas. Whether expression of p63 in breast correlates with tumor progression is the focus of this study. METHODS: Forty cases, which all contained normal breast tissue, ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma in the same patient were included in this investigation using an indirect immunohistochemical method and double staining. RESULTS: p63 was exclusively expressed in the myoepithelial cells of normal breast, partially expressed in ductal hyperplasia, rarely expressed in carcinoma in situ and not expressed in invasive carcinomas. CONCLUSION: The results suggest an association between loss of p63 expression and progression of breast ductal carcinoma. p63 immunostaining might be of assistance for distinguishing invasive ductal carcinoma from ductal carcinoma in situ or rare questionable ductal hyperplastic lesions, leading to correct therapy clinically.

Biopsy, Needle↗

PubMed2002

Heparanase: a key enzyme in invasion and metastasis of gastric carcinoma.

Previous reports have shown that the biochemical activity of heparanase is significantly correlated with the invasion and metastasis of malignant cells in vitro. Recently, it was found that the human heparanase gene was cloned and highly expressed in malignant cell lines and human solid malignant tumors. In the present study, we investigated the heparanase mRNA expression by using in situ hybridization in 116 paraffin-embedded tissues of primary gastric carcinomas. To explore its clinicopathologic significance, it was detected in the various steps of tumor progression and then compared with prognostic indicators. As a result, the heparanase expression was more prevalent in late-stage rather than early-stage carcinomas (P <.0001) and was more frequent in tumors of large size (P =.0212). Expression also correlated with lymphatic (P =.0086) and venous (P =.0171) invasion and with negative prognostic factors such as lymph nodal (P <.0001) and distant (P =.0221) metastases. However, in a multivariate analysis, messenger RNA expression of heparanase was not an independent prognostic factor. It was concluded that heparanase might play an important role in the development of invasion and metastasis of the gastric cancer. It was indicated that patients with heparanase-positive gastric carcinoma would have a greater chance of metastasis with a poor prognosis.

Female↗

PubMed2002

Helpful parameter for malignant potential of gastrointestinal stromal tumors (GIST).

BACKGROUND: Although a series of histopathological criteria have been suggested, the prediction of the malignant potential of gastrointestinal stromal tumors (GIST) is still difficult. The older literature called all gastrointestinal stromal tumors smooth muscle tumors or mixed GIST with true smooth muscle tumors. Reports on GIST including homogeneous cases were rare. METHODS: We examined 73 cases of GIST, which were immunohistochemically positive for c-kit and/or CD34, and mainly focused on the correlation between mitotic count and the other clinicopathological features to establish any helpful and reproducible parameters to indicate the malignant potential and to be used practically and objectively in the routine histopathological diagnosis of GIST. RESULTS: The results showed that there was a statistically significant difference in mitotic count between benign and malignant groups. Other proposed parameters, such as high cellularity, tumor size > or =5 cm, stomach and intestinal location, hemorrhage, necrosis, p53 expression and Ki-67 labeling index >10%, were frequently observed in tumors with mitotic figure. Three patients with one mitotic figure in 50HPF died from metastasis or recurrence of the tumors. CONCLUSIONS: Ki-67 index and cellularity should be used as predictors for the malignant potential of GIST. When other morphological features appear benign, mitotic count might also be a helpful practical factor in the prediction of the malignant potential of GIST.

Adolescent↗

PubMedDate not supplied

Loss of cell cohesion in breast cytology as a characteristic of neuroendocrine carcinoma.

OBJECTIVE: To characterize a specific group of breast cancers displaying a scattered single cell pattern in cytology and correlate it with histologic and immunohistochemical findings. STUDY DESIGN: Of 135 consecutive malignant breast cytologic specimens, 12 cases were selected for their scattered single cell pattern on aspiration cytology. Immunohistochemical staining for neuroendocrine markers and prognostic parameters was performed on paraffin sections of corresponding primary breast carcinomas. RESULTS: In the smears of the 12 cases, highly cellular neoplastic cells with a single cell pattern were observed predominantly. The tumor cells had relatively wide, granular cytoplasm and a low to moderate nuclear/cytoplasmic ratio. Histologically, they were arranged mainly in relatively large, solid nests and occasionally contained a tubular pattern with small amounts of stromal tissue. Five of the 12 cases demonstrated neuroendocrine differentiation with a positive immunoreaction for chromogranin A and synaptophysin. Except for the small mean size of the tumors (P < .01), no significant differences were identified among the prognostic parameters, including a nodal status, estrogen receptor status, growth fraction by Ki-67 or immunoreactivity for c-erbB-2, as compared with the other 123 cases. CONCLUSION: Loss of cell cohesion in breast cytology is a good morphologic marker for identifying neuroendocrine breast carcinoma.

Adult↗