Search PubMed⌕ Search

Biomedical subjects

Lin Zhang

Publications and source records attributed to Lin Zhang.

At least 55 records · Page 3Linked to original sources
PubMed2006

Tumor cell dormancy induced by p38SAPK and ER-stress signaling: an adaptive advantage for metastatic cells?

The mechanisms that determine whether a tumor cell that has disseminated to a secondary site will resume growth immediately, die or enter a state of dormancy are poorly understood. Although tumor dormancy represents a common clinical finding, studying the mechanisms behind this stage of tumor progression has been challenging. Furthermore, it is thought that dormant tumor cells are refractory to chemotherapy due to their lack of proliferation. However, whether this is the only reason for their chemo-resistance remains to be proven. In this review we summarize recent findings that provide a mechanistic explanation about how stress signaling through the p38(SAPK) pathway and ER-stress signaling may coordinate the induction of growth arrest and drug-resistance in a model of squamous carcinoma dormancy. We further discuss how dormant tumor cells may enter this stage to adapt to strenuous conditions that do not favor immediate growth after dissemination. Finally, we propose that this response may recapitulate an evolutionarily conserved program of life-span extension through adaptation and tolerance to stress.

Animals↗
PubMed2006

Haplotype of signal transducer and activator of transcription 3 gene predicts cardiovascular disease in dialysis patients.

Signal transducer and activator of transcription 3 (STAT3) protein has been linked to cardiovascular disease (CVD) through multiple pathways in experimental and animal studies. STAT3 gene variation was examined as a predictor of incident CVD in a subcohort of 529 incident white dialysis patients. Fifteen single-nucleotide polymorphisms of the STAT3 gene were genotyped. Haplotypes were estimated using software PHASE 2.1, and associations with first CVD event were tested using Cox proportional hazards analysis. Adjusted global tests of haplotype association with incident CVD and inflammation markers were performed using permutated P value in R-package Haplo.score. An a priori specified additive genetic model was assumed for haplotype analysis. Both genotypes (four single nucleotide polymorphisms with P < 0.001) and haplotypes (P = 0.002 overall) were associated with incident CVD. Two major haplotype blocks, blocks A and C, were identified. Compared with common haplotype A-1, A-3 was associated with a hazard ratio (HR) of 0.70 (95% confidence interval [CI] 0.51 to 0.94) for CVD events after adjustment for covariates including C-reactive protein (CRP) and interleukin 6. Compared with common haplotype C-1, C-3 was associated with an adjusted HR of 2.12 (95% CI 1.25 to 3.57) for CVD events. Associations were independent of inflammation markers, but IL-6 levels were 14% lower (geometric mean ratio 0.86; 95% CI 0.77 to 0.96) per copy of haplotype A-3 compared with haplotype A-1 in block A after adjustment for CRP and other risk factors (P = 0.008). Variation in the STAT3 gene is associated with the risk for CVD among white dialysis patients independent of serum IL-6 and CRP levels.

Aged↗
PubMed2006

[Surgery for scapular neck displaced fracture].

OBJECTIVE: To study the appropriate approach and method of fixation in the surgery for scapular neck displaced fracture. METHODS: Fourteen patients with serious step-off displacement of glenoid rim, with a distance of 3 cm (2 approximately 4 cm) involving fresh scapular neck fracture, all located from the superior scapular notch to glenoid armpit rim and passing through the mesoscapula, all of the type II according to the Miller's system, 10 males and 4 females, aged 33 (21 - 60). The surgical indications included a distance of step-off displacement exceeding 1 cm and a time between the injury and operation of 3 - 10 days. RESULTS: All operations were successful without injury of nerve and blood vessels. All the wounds obtained primary healing within 6 weeks (4 - 8 weeks). X-ray plain films showed that all cases obtained complete or nearly complete anatomical reduction. Follow-up carried out for 1 - 7 years showed no complication. According to the Hardegger's evaluation, 8 cases showed excellent prognosis, 4 showed good prognosis, and 2 showed fair prognosis. CONCLUSION: Operation is necessary for step-off displacement of glenoid rim involving scapular neck fracture. Hard and with regular shape, the mesoscapula and armpit rim suits for fixation. Open reduction through posterior approach and internal fixation in prone position help recover the morphology and biomechanics characteristic of scapula. Propitious to functional recovery, dirigation should begin early.

Adult↗
PubMed2006

A role for the mitogen-activated protein kinase kinase kinase 1 in epithelial wound healing.

The mitogen-activated protein kinase kinase (MEK) kinase 1 (MEKK1) mediates activin B signals required for eyelid epithelium morphogenesis during mouse fetal development. The present study investigates the role of MEKK1 in epithelial wound healing, another activin-regulated biological process. In a skin wound model, injury markedly stimulates MEKK1 expression and activity, which are in turn required for the expression of genes involved in extracellular matrix (ECM) homeostasis. MEKK1 ablation or down-regulation by interfering RNA significantly delays skin wound closure and impairs activation of Jun NH2-terminal kinases, induction of plasminogen activator inhibitor (PAI)-1, and restoration of cell-cell junctions of the wounded epidermis. Conversely, expression of wild-type MEKK1 accelerates reepithelialization of full-thickness skin and corneal debridement wounds by mechanisms involving epithelial cell migration, a cell function that is partially abolished by neutralizing antibodies for PAI-1 and metalloproteinase III. Our data suggest that MEKK1 transmits wound signals, leading to the transcriptional activation of genes involved in ECM homeostasis, epithelial cell migration, and wound reepithelialization.

Activins↗
PubMed2006

microRNAs exhibit high frequency genomic alterations in human cancer.

MicroRNAs (miRNAs) are endogenous noncoding RNAs, which negatively regulate gene expression. To determine genomewide miRNA DNA copy number abnormalities in cancer, 283 known human miRNA genes were analyzed by high-resolution array-based comparative genomic hybridization in 227 human ovarian cancer, breast cancer, and melanoma specimens. A high proportion of genomic loci containing miRNA genes exhibited DNA copy number alterations in ovarian cancer (37.1%), breast cancer (72.8%), and melanoma (85.9%), where copy number alterations observed in >15% tumors were considered significant for each miRNA gene. We identified 41 miRNA genes with gene copy number changes that were shared among the three cancer types (26 with gains and 15 with losses) as well as miRNA genes with copy number changes that were unique to each tumor type. Importantly, we show that miRNA copy changes correlate with miRNA expression. Finally, we identified high frequency copy number abnormalities of Dicer1, Argonaute2, and other miRNA-associated genes in breast and ovarian cancer as well as melanoma. These findings support the notion that copy number alterations of miRNAs and their regulatory genes are highly prevalent in cancer and may account partly for the frequent miRNA gene deregulation reported in several tumor types.

Breast Neoplasms↗
PubMed2006

Protective effects of minocycline on 3,4-methylenedioxymethamphetamine-induced neurotoxicity in serotonergic and dopaminergic neurons of mouse brain.

The repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) produces neurotoxicity in the 5-hydroxytryptamine (5-HT) and dopamine systems of the brain. In this study, we investigated the effects of minocycline, a second-generation tetracycline derivative, on MDMA-induced neurotoxicity in the 5-HT and dopaminergic systems of the mouse brain. The repeated administration of MDMA (10 mg/kg x 3, 3-h intervals, s.c.) significantly decreased the contents of 5-HT and its major metabolite 5-hydroxyindole acetic acid (5-HIAA) in the frontal cortex and hippocampus, and the density of the 5-HT transporter (5-HTT) in the frontal cortex, hippocampus and striatum. The repeated administration of MDMA (10 mg/kg x 3, 3-h intervals, s.c.) significantly decreased the contents of the dopamine and the density of the dopamine transporter (DAT) in the striatum, but not the frontal cortex. Furthermore, pretreatment and the subsequent administration of minocycline (40 mg/kg, i.p.) significantly attenuated the reduction of 5-HT and dopamine as well as the density of 5-HTT and DAT in the mouse brain by the repeated administration of MDMA. Moreover, pretreatment and the subsequent administration of minocycline (40 mg/kg) significantly attenuated the increase of activated microglia in the hippocampus and striatum after the repeated administration of MDMA. Our findings suggest that minocycline protects the neurotoxicity of the 5-HT and dopamine systems in the mouse brain after the administration of MDMA.

Animals↗
PubMed2006

Signature patterns revealed by microarray analyses of mice infected with influenza virus A and Streptococcus pneumoniae.

We used cDNA microarrays to identify differentially expressed genes in mice in response to infections with influenza virus A/PR/8/34 (H1N1) and Streptococcus pneumoniae. Expression microarray analysis showed up-regulation and down-regulation of many genes involved in the defense, inflammatory response and intracellular signaling pathways including chemokine, apoptosis, MAPK, Notch, Jak-STAT, T-cell receptor and complement and coagulation cascades. We have revealed signature patterns of gene expression in mice infected with two different classes of pathogens: influenza virus A and S. pneumoniae. Quantitative real-time RT-PCR results confirmed microarray results for most of the genes tested. These studies document clear differences in gene expression profiles between mice infected with influenza virus A and S. pneumoniae. Identification of genes that are differentially expressed after respiratory infections can provide insights into the mechanisms by which the host interacts with different pathogens, useful information about stage of diseases and selection of suitable targets for early diagnosis and treatments. The advantage of this novel approach is that the detection of pathogens is based on the differences in host gene expression profiles in response to different pathogens instead of detecting pathogens directly.

Animals↗
PubMed2006

[Clinical value of videomediastinoscopy in diagnosis of mediastinal disease].

OBJECTIVE: To evaluate the role of videomediastinoscopy in the diagnosis of disease of the mediastinum. METHODS: We retrospectively reviewed the clinical records of the 115 patients who underwent videomediastinoscopy. Local anesthesia or general anesthesia was employed. This operation consisted of cervical videomediastinoscopy in 102 patients, parasternal videomediastinoscopy in 13 patients, ninety-one patients had videomediastinoscopy for diagnosis of isolated mediastinal mass or lymphadenopathy, 25 patients with non small cell lung cancer or suspected lung cancer showed enlarged mediastinal lymph nodes radiographically in the chest. RESULTS: Among the patients with mediastinal disease, sarcoidosis was diagnosed in 37 patients, tuberculosis in 14 patients, lymphoma in 15 patients, nodal metastasis in 18 patients, noncaseating granulomata without classical "sarcoid" in 6 patients, with the accuracy of 93.3% (84/90); and staging of lung cancer in 25 patients, with the accuracy of 100% (25/25). The total accuracy of videomediastinoscoy and CT was 94.8% (109/115), 56.5% (65/115), respectively. Mean operative time was 26 min. There was neither complication nor mortality. CONCLUSION: videomediastinoscopy is a safe and effective procedure for the diagnosis of mediastinal disease and the staging of lung cancer.

Adolescent↗
PubMed2006

A neutral protease from Bacillus nematocida, another potential virulence factor in the infection against nematodes.

A neutral protease (npr) (designated Bae16) toxic to nematodes was purified to homogeneity from the strain Bacillus nematocida. The purified protease showed a molecular mass of approximately 40 kDa and displayed optimal activity at 55 degrees C, pH 6.5. Bioassay experiments demonstrated that this purified protease could destroy the nematode cuticle and its hydrolytic substrates included gelatin and collagen. The gene encoding Bae16 was cloned, and the deduced amino acid sequence showed 94% sequence identity with npr gene from B. amyloliquefaciens, but had low similarity (13-43%) with the previously reported virulence serine proteases from fungi or bacteria, which reflected their differences. Recombinant mature Bae16 (rm-Bae16) was expressed in Escherichia coli BL21 using pET30 vector system, and its nematicidal activity confirmed that Bae16 could be involved in the infection process. Our present study revealed that the npr besides the known alkaline serine protease could serve as a potential virulence factor in the infection against nematodes, furthermore, the two proteases with different characteristics produced by the same strain co-ordinated efforts to kill nematodes. These data helped to understand the interaction between this bacterial pathogen and its host.

Animals↗
PubMed2006

Integrative genomic analysis of protein kinase C (PKC) family identifies PKCiota as a biomarker and potential oncogene in ovarian carcinoma.

The protein kinase C (PKC) family plays a key regulatory role in a wide range of cellular functions as well as in various cancer-associated signal transduction pathways. Here, we investigated the genomic alteration and gene expression of most known PKC family members in human ovarian cancer. The DNA copy number of PKC family genes was screened by a high-resolution array-based comparative genomic hybridization in 89 human ovarian cancer specimens. Five PKC genes exhibited significant DNA copy number gains, including PKCiota (43.8%), PKCbeta1 (37.1%), PKCgamma (27.6%), PKCzeta (22.5%), and PKCtheta (21.3%). None of the PKC genes exhibited copy number loss. The mRNA expression level of PKC genes was analyzed by microarray retrieval approach. Two of the amplified PKC genes, PKCiota and PKCtheta, were significantly up-regulated in ovarian cancer compared with normal ovary. Increased PKCiota expression correlated with tumor stage or grade, and PKCiota overexpression was seen mostly in ovarian carcinoma but not in other solid tumors. The above results were further validated by real-time reverse transcription-PCR with 54 ovarian cancer specimens and 24 cell lines; overexpression of PKCiota protein was also confirmed by tissue array and Western blot. Interestingly, overexpressed PKCiota did not affect ovarian cancer cell proliferation or apoptosis in vitro. However, decreased PKCiota expression significantly reduced anchorage-independent growth of ovarian cancer cells, whereas overexpression of PKCiota contributed to murine ovarian surface epithelium transformation in cooperation with mutant Ras. We propose that PKCiota may serve as an oncogene and a biomarker of aggressive disease in human ovarian cancer.

Biomarkers, Tumor↗
PubMed2006

PUMA sensitizes lung cancer cells to chemotherapeutic agents and irradiation.

PURPOSE: Lung cancer, the leading cause of cancer mortality worldwide, is often diagnosed at late stages and responds poorly to conventional therapies, including chemotherapy and irradiation. A great majority of lung tumors are defective in the p53 pathway, which plays an important role in regulating apoptotic response to anticancer agents. PUMA was recently identified as an essential mediator of DNA damage-induced and p53-dependent apoptosis. In this study, we investigated whether the regulation of PUMA by anticancer agents is abrogated in lung cancer cells and whether PUMA expression suppresses growth of lung cancer cells and/or sensitizes lung cancer cells to chemotherapeutic agents and irradiation through induction of apoptosis. EXPERIMENTAL DESIGNS: The expression of PUMA was examined in lung cancer cells with different p53 status treated with chemotherapeutic agents. An adenovirus expressing PUMA (Ad-PUMA), alone or in combination with chemotherapeutic agents or gamma-irradiation, was used to treat lung cancer cells. The growth inhibitory and apoptotic effects of PUMA in vitro and in vivo were examined. The mechanisms of PUMA-mediated growth suppression and apoptosis were investigated through analysis of caspase activation and release of mitochondrial apoptogenic proteins. The cytotoxicities of PUMA on cancer and normal/nontransformed cells were compared. The efficacy of PUMA and p53 in suppressing the growth of lung cancer cells was also compared. RESULTS: We showed that the induction of PUMA by chemotherapeutic agents is abolished in p53-deficient lung cancer cells. PUMA expression resulted in potent growth suppression of lung cancer cells and suppressed xenograft tumor growth in vivo through induction of apoptosis. Low dose of Ad-PUMA significantly sensitized lung cancer cells to chemotherapeutic agents and gamma-irradiation through induction of apoptosis. The effects of PUMA are mediated by enhanced caspase activation and release of cytochrome c and apoptosis-inducing factor into the cytosol. Furthermore, PUMA seems to be selectively toxic to cancer cells and more efficient than p53 in suppressing lung cancer cell growth. CONCLUSIONS: Our findings indicate that PUMA is an important modulator of therapeutic responses of lung cancer cells and is potentially useful as a sensitizer in lung cancer therapy.

Animals↗
PubMed2006

Optic sensors of high refractive-index responsivity and low thermal cross sensitivity that use fiber Bragg gratings of >80 degrees tilted structures.

For the first time to the authors' knowledge, fiber Bragg gratings (FBGs) with >80 degrees tilted structures have been fabricated and characterized. Their performance in sensing temperature, strain, and the surrounding medium's refractive index was investigated. In comparison with normal FBGs and long-period gratings (LPGs), >80 degrees tilted FBGs exhibit significantly higher refractive-index responsivity and lower thermal cross sensitivity. When the grating sensor was used to detect changes in refractive index, a responsivity as high as 340 nm/refractive-index unit near an index of 1.33 was demonstrated, which is three times higher than that of conventional LPGs.

Journal Article↗
PubMed2006

The role of 11C-choline positron emission tomography-computed tomography and videomediastinoscopy in the evaluation of diseases of middle mediastinum.

BACKGROUND: Middle mediastinal masses comprise a wide variety of tumors but may also reflect lymphadenopathy, and thus remain an interesting diagnostic challenge. We performed positron emission tomography (PET) of mediastinal masses in order to evaluate the ability of PET to predict the malignancy of these tumors. We compared histologic findings, videomediastinoscopy, computed tomography (CT), and PET-CT in patients with mediastinal disease. METHODS: Thirty-two patients were evaluated with CT, PET-CT and videomediastionoscopy, and all studies were performed within four weeks in each patient. (11)C-choline as a PET tracer was used to visualize masses. PET data were evaluated using the standardized uptake value (SUV) and were compared with pathologic data. RESULTS: There were 13 men and 19 women aged from 21 to 74 (mean 45.2) years. Among the patients with mediastinal diseases, sarcoidosis was diagnosed in 12 patients, tuberculosis in 5 patients, lymphoma in 5 patients, and noncaseating granulomata without classical "sarcoid" finding in 3 patients. N2 or N3 nodal metastasis was revealed in 6 of 7 patients who had non-small cell lung cancer or suspected lung cancer, and one was negative (the pathological diagnosis was reactive hyperplasia). The accuracies for correctly diagnosing mediastinal masses for CT, PET-CT and videomediastinoscopy were 38% (12/32), 63% (20/32), and 91% (29/32) respectively. The diagnostic accuracy of videomediastinoscopy was superior to that of PET-CT (chi(2) = 11.130, P < 0.001). The SUVs were similar among these diseases. On the other hand, if the diagnostic classification was benign vs malignancy, the accuracies for CT, PET-CT and videomediastinoscopy were 53% (17/32), 75% (24/32), 100% (32/32) respectively. The diagnostic accuracy of videomediastinoscopy was superior to that of PET-CT (chi(2) = 22.042, P < 0.001). The SUV of malignant lesions (6.9, 3.2 - 9.8; n = 11) appeared to be higher than that of benign lesions (4.9, 2.9 - 8.3; n = 21), however, this difference was not statistically significant (P = 0.054). CONCLUSIONS: To diagnose lesions located in the middle mediastinum, videomediastinoscopy possesses the highest diagnostic accuracy, and therefore remains the gold standard. PET-CT is valuable for differential diagnosis of benign vs malignant lesions, CT alone or PET alone (SUV) may provide misdiagnosis in a substantial proportion of patients with mediastinal masses.

Adult↗
PubMed2006

PUMA Dissociates Bax and Bcl-X(L) to induce apoptosis in colon cancer cells.

PUMA is a BH3-only Bcl-2 family protein that plays an essential role in DNA damage-induced apoptosis. PUMA interacts with anti-apoptotic Bcl-2 and Bcl-X(L) and is dependent on Bax to induce apoptosis. In this study, we investigated how the interactions of PUMA with the antiapoptotic proteins coordinate with Bax to initiate apoptosis in HCT116 colon cancer cells. We found that Bcl-X(L) was most effective among several antiapoptotic proteins in suppressing PUMA-induced apoptosis and PUMA-dependent apoptosis induced by the DNA-damaging agent adriamycin. Mutant Bcl-X(L) that cannot interact with Bax was unable to protect cells from PUMA-mediated apoptosis. Knockdown of Bcl-X(L) by RNA interference significantly enhanced PUMA-mediated apoptosis in HCT116 cells but not in PUMA-knockout cells. Furthermore, Bax was found to be dissociated preferentially from Bcl-X(L) in HCT116 cells but not in the PUMA-knockout cells, in response to PUMA induction and adriamycin treatment. PUMA inhibited the association of Bax and Bcl-X(L) in vitro by directly binding to Bcl-X(L) through its BH3 domain. Finally, we found that wild-type Bax, but not mutant Bax deficient in either multimerization or mitochondrial localization, was able to restore PUMA-induced apoptosis in the BAX-knockout cells. Together, these results indicate that PUMA initiates apoptosis in part by dissociating Bax and Bcl-X(L), thereby promoting Bax multimerization and mitochondrial translocation.

Amino Acid Sequence↗
PubMed2006

Administration of PUMA adenovirus increases the sensitivity of esophageal cancer cells to anticancer drugs.

Esophageal cancer is one of the most lethal human tumors, characterized by relative chemoresistance and poor prognosis. Researchers have been seeking for multimodality to improve its outcome of therapy. PUMA (p53 upregulated modulator of apoptosis) is a potent proapoptotic molecule that is rapidly induced in cells following DNA damage and is required for p53-induced apoptosis. We evaluated the therapeutic potential of PUMA adenovirus against esophageal cancer cell lines (KYSE-150, KYSE-410, KYSE-510 and YES-2). Infection with Ad-PUMA (PUMA Adenovirus) resulted in the more powerful cytotoxicity in these cell lines compared with Ad-p53. Furthermore, we assessed the efficacy of a combined treatment with Ad-PUMA and anticancer drug (cisplatin, paclitaxel, 5-fluorouracil, respectively) for these cells and found PUMA significantly increased the chemosensitivity of esophageal cancer cells, which may result from more abundant apoptosis induction. Interestingly, Ad-PUMA was found to be more efficient than Ad-p53 in inhibiting cell growth and enhancing the chemosensitivity of esophageal cancer cell lines irrespective of the p53 status. These results suggest that Ad-PUMA is a potent cytotoxic agent and could be a promising alternative in the cancer gene therapy in combination with chemotherapeutic agents.

Antineoplastic Agents↗
PubMed2006

[Resection for lung cancer invading the superior vena cava].

OBJECTIVE: To analyze the feasibility and the value of resection for lung cancer invading the superior vena cava (SVC). METHODS: Between 1988 and 2005 the data of 31 patients who underwent resection were analyzed retrospectively. The reconstruction was done using simple suture, pericardial patch or prosthetic replacement. Postoperative morbidity, long-term survival were examined using the Kaplan-Meier method (Log rank test) and the COX model for survival. RESULTS: Seventeen squamous cell carcinomas, 8 adenocarcinomas, and 6 undifferentiated small cell carcinomas were resected. There were 13 partial SVC resection, the reconstruction was done using a simple running in 5 patients, and a pericardial patch in 8 patients. Eighteen patients underwent complete resection of SVC with prosthetic replacement. The time of clamping the SVC system was from 8 to 35 minutes for complete resection patients, while the time was from 3 to 15 minutes for partial resection patients. One patient didn't clamp the SVC. Postoperative morbidity and mortality were 48% and 0%, respectively. One, 3 and 5-year survival rates were 61%, 33% and 21%, respectively, with median survival at 31 months. Survival rate of patients with N2 disease was obviously lower than those with localized (N0/N1) nodal disease (chi2 = 14.3, P = 0.000), the median survival was 42 and 13 months respectively. There were no significant effects on overall survival with pathologic features and surgery methods. Survival rate of patients with induction chemotherapy before operation or intraoperative chemotherapy was higher than those received direct surgery (chi2 = 5.0, P = 0.025), the median survival was 39 and 14 months respectively. CONCLUSIONS: The resection of the SVC for involvement by lung cancer can be performed in selected patients, especially for those with localized (N0/N1) nodal disease. Induction chemotherapy should be performed.

Adult↗
PubMed2006

Complex wurtzite ZnSe microspheres with high hierarchy and their optical properties.

Complex wurtzite ZnSe microspheres with hierarchical fractal structure and showing strong quantum-size effects can be prepared easily by a mild solvothermal reaction in a diethylenetriamine (DETA)-deionized water (DIW) binary solution. The ZnSe microspheres are made up of nanosheets, each formed by the face-to-face pairing of two individual nanosheets. In addition, high-order, flowerlike hierarchical structures are formed by the attachment of flexible, uniform nanofibers to the exposed faces of each nanosheet pair. The surface morphology of the nanosheets changed as reaction time increased and the detailed phase-transformation and shape-evolution processes were studied. This approach could provide an effective strategy for tuning the electronic and optical properties of semiconductors, with special advantages over the traditional high-temperature approach, and could be extended to access other semiconductor materials with unusual morphologies and structures.

Journal Article↗