PubMed Health⌕ Search

Biomedical subjects

Jinsong Liu

Publications and source records attributed to Jinsong Liu.

17 recordsLinked to original sources
PubMed2003

Silencing of H-ras gene expression by retrovirus-mediated siRNA decreases transformation efficiency and tumorgrowth in a model of human ovarian cancer.

To examine the role of H-ras in the development of human ovarian cancer, we used small inhibitory RNA (siRNA) to silence its expression in human ovarian cancer cell lines and assessed the effects of its silencing on proliferation, apoptosis, and tumorgrowth. First, we developed a retrovirus-based delivery system that allowed long-term stable expression of the desired siRNA. Retrovirus-mediated expression of siRNA against green fluorescence protein (GFP) reduced its expression more than 90% in four cancer cell lines. We then constructed three retroviruses that expressed siRNAs targeting the H-rasV(12) mutation (H1/siRNA) or either of two wild-type sequences of the H-ras gene (H2/siRNA and H3/siRNA) and used these retroviruses to infect T80H and SKOV-3 cells. In T80H cells (a genetically transformed human ovarian surface epithelial cell line whose tumorigenicity depends on H-rasV(12) expression), infection with the H1/siRNA and H2/siRNA, but not with H3/siRNA, decreased T80H proliferation, increased G(0)/G(1) arrest and apoptosis, blocked transformation in vitro, and suppressed tumor growth in nude mice. In SKOV-3 cells (a human ovarian cancer cell line that contains high levels of wild-type H-ras protein but no H-rasV(12) mutation), introduction of the H2/siRNA construct, but not H1/siRNA or H3/siRNA, produced similar effects, demonstrating that the suppression of tumorgrowth by siRNA was sequence-specific. We conclude that H-ras is involved in maintenance of tumorgrowth of human ovarian cancer, and that retrovirus-mediated siRNA expression against H-ras expression is a powerful tool to dissect ras-signaling pathways and may be used therapeutically against ovarian cancer.

Animals↗
PubMed2003

Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptors.

Members of the nuclear receptor (NR) superfamily of transcription factors modulate gene transcription in response to small lipophilic molecules. Transcriptional activity is regulated by ligands binding to the carboxy-terminal ligand-binding domains (LBDs) of cognate NRs. A subgroup of NRs referred to as 'orphan receptors' lack identified ligands, however, raising issues about the function of their LBDs. Here we report the crystal structure of the LBD of the orphan receptor Nurr1 at 2.2 A resolution. The Nurr1 LBD adopts a canonical protein fold resembling that of agonist-bound, transcriptionally active LBDs in NRs, but the structure has two distinctive features. First, the Nurr1 LBD contains no cavity as a result of the tight packing of side chains from several bulky hydrophobic residues in the region normally occupied by ligands. Second, Nurr1 lacks a 'classical' binding site for coactivators. Despite these differences, the Nurr1 LBD can be regulated in mammalian cells. Notably, transcriptional activity is correlated with the Nurr1 LBD adopting a more stable conformation. Our findings highlight a unique structural class of NRs and define a model for ligand-independent NR function.

Binding Sites↗
PubMed2003

Role of BRCA1 in cellular resistance to paclitaxel and ionizing radiation in an ovarian cancer cell line carrying a defective BRCA1.

BRCA1, the gene responsible for approximately half of all cases of hereditary breast cancer and almost all cases of combined hereditary breast and ovarian cancer, has been implicated in the maintenance of genomic stability through DNA repair. This function is mediated, at least in part, through two tandem BRCA1 C-terminal (BRCT) repeats. The role of BRCA1 in the development of ovarian cancer is poorly understood, partially owing to the lack of ovarian cancer cell lines with defective BRCA1. The purpose of this study was to further characterize an endometrioid ovarian cancer cell line, SNU-251, which was previously reported to carry a nonsense mutation (from G to A) at amino acid 1815 of BRCA1. In addition, we examined the role of BRCA1 in the cell cycle and in the responses to the chemotherapy drug paclitaxel and ionizing radiation. Loss of the C-terminal 49 amino acids due to this point mutation did not affect the expression of the truncated BRCA1 protein, but caused a loss of transcriptional activation of the endogenous p21(WAF1/CIP1) gene, and could not sustain arrest in the G(2)/M phase of the cell cycle. The BRCA1 mutation in SNU-251 cells inhibited BRCA1 subnuclear assembly for DNA-damage repair and increased cellular sensitivity to ionizing radiation and paclitaxel. This sensitivity was reversed by reintroduction of ectopic wild-type BRCA1. Our results suggest that the deletion of the C-terminal 49 amino acids of BRCA1 results in a loss of BRCA1 function in the SNU-251 cell line. BRCA1 helps to mediate the resistance to both radiation and paclitaxel. Therefore, SNU-251 may be a useful model for studying the molecular mechanism of BRCA1 in the resistance of ovarian cancer to ionizing radiation and chemotherapy treatment and in the development of hereditary human ovarian cancer.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Inhibition of human telomerase reverse transcriptase gene expression by BRCA1 in human ovarian cancer cells.

Human telomerase reverse transcriptase (hTERT), the catalytic subunit of human telomerase, is responsible for the synthesis and maintenance of the telomeric repeats at the distal ends of human chromosomes. Telomerase expression is repressed in normal human cells and is activated in immortal cells and during tumorigenesis, but the mechanism by which telomerase expression is regulated is not fully understood. Previous studies have shown that c-Myc stimulates hTERT transcription through the binding sites located on the hTERT promoter. In this study, we sought to determine whether BRCA1 inhibits hTERT transcription through its direct interaction with c-Myc. In ovarian cancer cells, c-Myc increased hTERT expression by threefold and BRCA1 completely abrogated this activity. A mutation in the c-Myc-binding site (E-box) of the hTERT promoter resulted in the loss of activation by c-Myc and in the loss of inhibition by BRCA1. Deletion of the c-Myc-binding domain in BRCA1 resulted in the loss of BRCA1's ability to inhibit transcription of the hTERT promoter. In addition, BRCA1 associates with c-Myc and inhibits the binding activity of c-Myc to the hTERT promoter. Our data indicate that BRCA1 is involved in regulating cellular immortalization through the modulation of c-Myc on the hTERT promoter.

BRCA1 Protein↗
PubMed2003

Benign cystic mesothelioma of the peritoneum: a clinicopathologic study of 17 cases and immunohistochemical analysis of estrogen and progesterone receptor status.

Benign cystic mesothelioma (BCM) is an uncommon lesion of the peritoneum occurring predominantly in women of reproductive age. Although most patients are managed by surgical resection, a reported high incidence of cyst recurrence has led to the use of hormonal therapy in isolated cases in an attempt to control cyst size and relieve local symptoms. To date, the estrogen receptor (ER) and progesterone receptor (PR) status of BCM has not been evaluated. Here we present our experience with 17 cases (13 women, 4 men) of BCM seen over a 19-year period, including an immunohistochemical analysis of ER and PR status in 14 cases. All lesions showed typical morphological features of BCM, and calretinin immunostaining was positive in 14 of 14 cases. Five patients experienced either 1 or 2 tumor recurrences, and no patients died of disease. One case was diffusely positive for ER only, 1 case was focally positive for PR only, and 1 case was focally positive for both ER and PR. Although immunohistochemical detection of female sex hormone receptors in BCM is uncommon, the focal presence of ER and/or PR in some lesions does provide weak biologic support for the use of hormonal manipulation as a therapeutic option. Hum Pathol 34:369-374.

Adolescent↗
PubMed2003

Tissue macroarray: a simple and cost-effective method for high-throughput studies.

The tissue microarray technique is a powerful technique that can examine many clinical specimens in a single slide. However, this technique requires a specialized instrument for the construction of tissue microarray block. The authors describe an alternative tissue macroarray technique for the simultaneous analysis of multiple clinical specimens on a single slide. As an example of this method, the authors assembled 12 tumor samples from 12 different paraffin blocks on a glass slide and then immunostained with hMLH1 antibody. This simple method does not need specialized equipment and should be an alternative efficient approach for large-scale clinical specimens.

Antibodies, Monoclonal↗
PubMed2003

Ovarian sex cord-stromal tumors: an immunohistochemical study including a comparison of calretinin and inhibin.

Because ovarian sex cord-stromal tumors (SCST) are morphologically heterogeneous neoplasms that are relatively infrequently encountered, their diagnosis can be difficult. Immunohistochemical staining may be useful for establishing the diagnosis in problematic cases. We studied 53 ovarian SCSTs to characterize their immunohistochemical staining pattern: 17 adult granulosa cell tumors (AGCTs), 4 juvenile granulosa cell tumors (JGCTs), 3 sex cord tumors with annular tubules (SCTATs), 9 Sertoli-Leydig cell tumors (SLCTs), 10 fibromas, 5 fibrothecomas (FTs), and 5 thecomas. In 8 of the 53 cases, the tissue studied was from a metastatic site. The immunopanel included calretinin, inhibin, WT1, cytokeratin cocktail, epithelial membrane antigen (EMA), and cytokeratin 5/6 (CK5/6). The fibromas and FTs were also tested with CD10. The extent of staining was assessed in a semiquantitative fashion and ranked on a scale of 0 through 4+. All of the tumors, except for 1 metastatic SLCT, were positive for calretinin. Forty-five of the cases (85%) stained for inhibin; 1 metastatic AGCT, 3 fibromas, and 4 FTs were negative. WT1 was present in 39 tumors (74%), with expression most prominent in the SLCTs. The cytokeratin cocktail stained 23 of the 53 tumors (43%), whereas just 1 tumor was positive for EMA (1+ in a JGCT). All tumors were negative for CK5/6, and the 15 fibromas and FTs were negative for CD10. We conclude that because cytokeratin is frequently expressed by SCSTs, in particular by granulosa cell tumors, SLCTs, and SCTATs, the inclusion of EMA in a panel may help to exclude epithelial neoplasms. In addition, WT1, present in normal granulosa cells, is expressed by a majority of SCSTs. Finally, these results demonstrate that calretinin is at least as sensitive as inhibin for ovarian SCSTs overall and that it is more sensitive than inhibin for fibromas and FTs.

Biomarkers, Tumor↗
PubMed2003

Uterine tumor resembling ovarian sex-cord tumor: report of a case mimicking cervical adenocarcinoma.

Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are unusual neoplasms with histologic features that resemble those within ovarian Sertoli and granulosa cell tumors. We report the case of a 24-year-old woman with a UTROSCT presenting as a cervical mass, which on initial evaluation was thought to represent cervical adenocarcinoma. The patient's cervical biopsy specimen contained epithelioid cells arranged in tubules and anastomosing cords, without significant cellular atypia or mitotic activity. Because this morphology elicited a broad differential diagnosis, immunohistochemical studies were performed. The tumor was found to be diffusely positive for cytokeratin cocktail, calretinin, and desmin, focally positive for CK7 and SMA, and negative for EMA, CEA, inhibin, CD10, CK20, chromogranin, and synaptophysin. Ultrastructural examination revealed occasional gland-like lumens with cells joined by desmosomes and a continuous basal lamina. UTROSCTs have features that may cause them to be confused with more common tumors, especially in limited biopsy samples, and should be included in the differential diagnosis when a gland-forming neoplasm with an unusual appearance is identified in a cervical or endometrial biopsy specimen.

Actins↗
PubMed2003

Cell to cell contact required for bystander effect of the TNF-related apoptosis-inducing ligand (TRAIL) gene.

We have previously reported that direct transfer of the TNF-related apoptosis-inducing ligand (TRAIL) gene resulted in an apoptotic bystander effect, and that this bystander effect was not transferable with cell culture media. To further characterize its mechanism we tested the bystander effect of TRAIL in the human ovarian cancer cell line DOV13, human lung cancer cell line A549, human hepatoma cell line Hepa G2, human breast cancer cell line MDA-MB231 and human colon cancer cell lines Lovo and DLD1. The bystander target cells were transduced with an adenovector expressing the lacZ gene (Ad/CMV-LacZ), while the effector cells were transduced with an adenovector expressing the green fluorescent protein (GFP)/TRAIL fusion gene. Effector and target cells were then cocultured in the same well with or without effector and target cell contact. In all the cell lines tested, target cells were killed if effector and target cell contact was permitted. However, no bystander effect occurred if effector and target cell contact was prevented. Furthermore, the bystander effect and apoptosis induction of TRAIL was dramatically reduced if cells were seeded at a very low density. Moreover, in all the cell lines tested, no detectable soluble TRAIL was found in media from the TRAIL-expressing cell cultures. Together, our results demonstrated that release of soluble TRAIL from transfer of the wild-type TRAIL gene is minimal, and that the bystander effect of the TRAIL gene is mainly mediated by membrane-bound TRAIL on the surface of transduced cells.

Apoptosis↗
PubMed2002

The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo.

The Period2 gene plays a key role in controlling circadian rhythm in mice. We report here that mice deficient in the mPer2 gene are cancer prone. After gamma radiation, these mice show a marked increase in tumor development and reduced apoptosis in thymocytes. The core circadian genes are induced by gamma radiation in wild-type mice but not in mPer2 mutant mice. Temporal expression of genes involved in cell cycle regulation and tumor suppression, such as Cyclin D1, Cyclin A, Mdm-2, and Gadd45alpha, is deregulated in mPer2 mutant mice. In particular, the transcription of c-myc is controlled directly by circadian regulators and is deregulated in the mPer2 mutant. Our studies suggest that the mPer2 gene functions in tumor suppression by regulating DNA damage-responsive pathways.

ARNTL Transcription Factors↗
PubMed2002

Structural basis of transcription activation: the CAP-alpha CTD-DNA complex.

The Escherichia coli catabolite activator protein (CAP) activates transcription at P(lac), P(gal), and other promoters through interactions with the RNA polymerase alpha subunit carboxyl-terminal domain (alphaCTD). We determined the crystal structure of the CAP-alphaCTD-DNA complex at a resolution of 3.1 angstroms. CAP makes direct protein-protein interactions with alphaCTD, and alphaCTD makes direct protein-DNA interactions with the DNA segment adjacent to the DNA site for CAP. There are no large-scale conformational changes in CAP and alphaCTD, and the interface between CAP and alphaCTD is small. These findings are consistent with the proposal that activation involves a simple "recruitment" mechanism.

Crystallography, X-Ray↗
PubMed2002

Evolution of separate screening soliton pairs in a biased series photorefractive crystal circuit.

This paper presents calculations for an idea in photorefractive spatial soliton, namely, screening solitons form in a biased series photorefractive crystal circuit consisting of two photorefractive crystals connected electronically by electrode leads in a chain with a voltage source. A system of two coupled equations is derived under appropriate conditions for two-beam propagation in the crystal circuit. The possibility of obtaining steady-state bright and dark screening soliton solutions is investigated in one dimension and, the existence of dark-dark, bright-dark, and bright-bright separate screening soliton pairs in such a circuit is proved. The numerical results show that the two solitons in a soliton pair can affect each other by the light-induced current and their coupling can affect their spatial profiles, dynamical evolutions, stabilities, and self-deflection. Under the limit in which the optical wave has a spatial extent much less than the width of the crystal, only the dark soliton can affect the other soliton by the light-induced current, but the bright soliton cannot. For a bright-dark or dark-dark soliton pair, the dark soliton in a weak input intensity can be obtained for a larger nonlinearity than for a stronger input intensity. For a bright-dark soliton pair, increasing the input intensity of the dark soliton can increase the bending angle of the bright soliton. Some potential applications are discussed.

Journal Article↗
PubMed2002

A draft sequence of the rice genome (Oryza sativa L. ssp. indica).

We have produced a draft sequence of the rice genome for the most widely cultivated subspecies in China, Oryza sativa L. ssp. indica, by whole-genome shotgun sequencing. The genome was 466 megabases in size, with an estimated 46,022 to 55,615 genes. Functional coverage in the assembled sequences was 92.0%. About 42.2% of the genome was in exact 20-nucleotide oligomer repeats, and most of the transposons were in the intergenic regions between genes. Although 80.6% of predicted Arabidopsis thaliana genes had a homolog in rice, only 49.4% of predicted rice genes had a homolog in A. thaliana. The large proportion of rice genes with no recognizable homologs is due to a gradient in the GC content of rice coding sequences.

Arabidopsis↗
PubMed2002

Dynamics of pharmaceutical amorphous solids: the study of enthalpy relaxation by isothermal microcalorimetry.

The structural relaxation time is a measure of the molecular mobility involved in enthalpy relaxation, and thus, is a measure of the dynamics of amorphous (glassy) pharmaceutical solids that determines physicochemical properties and reactivity of drugs in amorphous formulations. In this article we describe a novel method for characterization of structural relaxation using isothermal microcalorimetry, which directly measures the rate of heat release during the relaxation processes. The structural relaxation time is then obtained from a fit of the power data to the derivative version of the Kohlrausch-Williams-Watts (KWW) equation. The relaxation times of quenched and lyophilized samples of saccharides were studied using an isothermal microcalorimeter, the Thermal Activity Monitor (TAM). In addition to the KWW derivative function, a derivative equation of the modified stretched exponential function (MSE) was employed to evaluate TAM data. The later (MSE) appeared to have numerical advantages over the KWW equation. The data demonstrate, as expected, that structural relaxation times of amorphous solids depend on a number of variables, including nature of material, temperature, moisture content, thermal history, etc. Isothermal microcalorimetry with the TAM provides a very fast and reliable way to characterize the dynamics of glassy materials, which in many respects is superior to the conventional DSC approach. To the extent stability and structural relaxation dynamics in the glass are correlated, structural relaxation parameters derived by isothermal microcalorimetry may provide data useful for rational development of stable peptide and protein formulations and for the control of their processing.

Algorithms↗
PubMed2002

Wolffian duct tumors: case reports and review of the literature.

BACKGROUND: Female adnexal tumors of probable wolffian origin are a distinctive epithelial neoplasm arising from the remnants of the mesonephric duct. Although generally considered a tumor of low malignant potential, these tumors can recur. Two cases are reported here. CASES: (1) A 38-year-old G(6)P(6) Latin American woman presented with lower abdominal pain and a pelvic mass. She had a history of a total abdominal hysterectomy and bilateral salpingo-oophorectomy with a paratubal nodule found incidentally 3 years prior. The pathologic findings were consistent with a female adnexal tumor of probable wolffian origin. Imaging studies revealed significant metastatic disease throughout her abdomen and pelvis. The recurrence was confirmed at laparotomy and tumor debulking was performed. Four months later the patient suffered a second recurrence and is currently undergoing treatment with systemic therapy. (2) A 71-year-old Caucasian woman who had undergone exploratory laparotomy and tumor reductive surgery for a female adnexal tumor of probable wolffian duct origin was seen for routine evaluation 1 year after her surgery. Her computed tomography scan revealed possible evidence of recurrence. CONCLUSION: Most female adnexal tumors of wolffian origin behave in a benign fashion. However, there is a potential risk of recurrence. Surgical excision by total abdominal hysterectomy and bilateral salpingo-oophorectomy at the time of diagnosis may be the best recommended mode of therapy. The role of adjuvant radiation therapy or chemotherapy remains questionable.

Adult↗